Isabel Coma-Canella

Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test

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.

The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus

BackgroundPatients 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.MethodsIn 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.ResultsDPP4a 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).ConclusionsAn 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.

Changes in plasma potassium during the dobutamine stress test

We performed serial determinations of levels of potassium in 198 patients with suspected or proven coronary arterial disease who underwent a dobutamine stress test, so as to investigate if the depression in the ST segment induced by the test may be due to hypokalemia. The test consisted of an intravenous infusion of dobutamine, starting with a dose of 5 micrograms/kg/min for 5 minutes and continuing with 10, 15, 20 and up to 40 micrograms/kg/min every 5 minutes (mean peak dose = 20 micrograms/kg/min). Serial 12-lead electrocardiograms were taken to detect changes in the ST segment. The double product changed with dobutamine from 8844 +/- 6000 to 15201 +/- 3030. The peak dose of dobutamine induced a small but significant decrease in levels of serum potassium, with a further decrease 10 minutes later. In the 198 patients, the plasma potassium changes from 4.22 +/- 4.8 to 3.86 +/- 0.35 mmol/l (P less than 0.00001). The maximum decrease in potassium (0.56 +/- 0.49) occurred in the patients who received the highest dose of dobutamine (30 to 40 micrograms/kg/min). Only 17 patients reached levels lower than 3.5 mmol/l, and 4 of them achieved levels lower than 3.1 mmol/l. No correlation was found between depression of the ST segment equal to or greater than 1 mm on the electrocardiogram and the level of potassium after the test. No correlation was found between ventricular arrhythmias and levels of potassium. High doses of dobutamine, therefore, produce a small but significant decrease in potassium.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized clinical trial on acute effects of i.v. iron sucrose during haemodialysis

Aim:  Haemodialysis induces endothelial dysfunction by oxidation and inflammation. Intravenous iron administration during haemodialysis could worsen endothelial dysfunction. The aim of this study was to ascertain if iron produces endothelial dysfunction and the possible neutralizing effect of N‐acetylcysteine when infused before iron. The oxidative and inflammatory effects of iron during haemodialysis were also assessed.

Association of low GLP-1 with oxidative stress is related to cardiac disease and outcome in patients with type 2 diabetes mellitus: A pilot study

Oxidative stress (OS) contributes to cardiovascular damage in type 2 diabetes mellitus (T2DM). The peptide glucagon-like peptide-1 (GLP-1) inhibits OS and exerts cardiovascular protective actions. Our aim was to investigate whether cardiac remodeling (CR) and cardiovascular events (CVE) are associated with circulating GLP-1 and biomarkers of OS in T2DM patients. We also studied GLP-1 antioxidant effects in a model of cardiomyocyte lipotoxicity. We examined 72 T2DM patients with no coronary or valve heart disease and 14 nondiabetic subjects. A median of 6 years follow-up information was obtained in 60 patients. Circulating GLP-1, dipeptidyl peptidase-4 activity, and biomarkers of OS were quantified. In T2DM patients, circulating GLP-1 decreased and OS biomarkers increased, compared with nondiabetics. Plasma GLP-1 was inversely correlated with serum 3-nitrotyrosine in T2DM patients. Patients showing high circulating 3-nitrotyrosine and low GLP-1 levels exhibited CR and higher risk for CVE, compared to the remaining patients. In palmitate-stimulated HL-1 cardiomyocytes, GLP-1 reduced cytosolic and mitochondrial oxidative stress, increased mitochondrial ATP synthase expression, partially restored mitochondrial membrane permeability and cytochrome c oxidase activity, blunted leakage of creatine to the extracellular medium, and inhibited oxidative damage in total and mitochondrial DNA. These results suggest that T2DM patients with reduced circulating GLP-1 and exacerbated OS may exhibit CR and be at higher risk for CVE. In addition, GLP-1 exerts antioxidant effects in HL-1 palmitate-overloaded cardiomyocytes. It is proposed that therapies aimed to increase GLP-1 may counteract OS, protect from CR, and prevent CVE in patients with T2DM.

Disminución de la reserva de flujo coronario en pacientes con insuficiencia cardíaca no isquémica

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.

Characterization of coronary plaques with combined use of intravascular ultrasound, virtual histology and optical coherence tomography.

According to post-mortem studies, luminal thrombosis occurs from plaque rupture, erosion and calcified nodules. In vivo studies have found thin cap fibroatheroma (TCFA) as the main vulnerable lesion, prone to rupture. Few data about other post-mortem lesions have been reported in vivo. Our main objective is to characterize in vivo the coronary plaques with intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT), in order to detect not only thin cap fibroatheroma (TCFA), but also other possible vulnerable lesions. The secondary objective is to correlate these findings with clinical and analytical data. Twenty-five patients (18 stable) submitted to coronary angiography were included in this pilot study. After angiography, the three vessels were studied (when possible) with IVUS-VH and OCT. Plaque characteristics were correlated with clinical and analytical data. Forty-six lesions were analyzed. IVUS-VH detected significant necrotic core in 15 (3 were definite TCFA). OCT detected TCFA in 10 lesions, erosion in 6, thrombus in 5 and calcified nodule in 8. Possible vulnerable lesion was found in 61% of stable and 57% of unstable patients. Erosions and calcified nodules were only found in stable patients. Those with significant necrotic core had higher body mass index (P=0.016), higher levels of hs-CRP (P=0.019) and triglycerides (P=0.040). The higher the levels of hs-CRP, the larger the size of the necrotic core (r=0.69, P=0.003). Lesions with characteristics of vulnerability were detected by IVUS-VH and OCT in more than 50% of stable and unstable coronary patients. A significant necrotic core was mainly correlated with higher hs-CRP.

Ventriculografía isotópica en voluntarios jóvenes sanos. Respuesta a diferentes tipos de estrés

Introduccion y objetivos Debido al uso creciente del estres farmacologico y la falta de estudios comparativos de funcion ventricular, nos propusimos conocer los limites normales de funcion ventricular con diferentes tipos de estres y comparar la respuesta entre ellos. Metodos Se diseno un ensayo clinico aleatorizado, abierto, controlado, en 4 grupos paralelos y en fase II. Se incluyeron 40 varones voluntarios sanos de edades comprendidas entre 18 y 25 anos que fueron aleatorizados en 4 grupos de 10 sujetoscada uno: ejercicio fisico (grupo 1), dobutamina (grupo 2), trifosfato de adenosina (ATP) (grupo 3) y dipiridamol (grupo 4). Cada voluntario fue estudiado mediante ventriculografia isotopica de equilibrio, en reposo y durante el estres. Resultados La fraccion de eyeccion global y regional aumento significativamente con los 4 tipos de estres, teniendo lugar el aumento maximo con dobutamina y el minimo con dipiridamol. El ejercicio fisico produjo un incremento de la fraccion de eyeccion global del 13 ± 5%; la dobutamina del 16 ± 6%; el ATP del 9 ± 3%, y el dipiridamol del 4 ± 3%. Conclusiones En sujetos jovenes sanos la fraccion de eyeccion global y regional aumenta de forma significativamente superior con dobutamina que con los otros tipos de estres. Con dipiridamol se obtiene el minimo aumento.

Estudio ecocardiográfico y de la concentración de NT-proBNP en pacientes diabéticos tipo 2 con y sin cardiopatía isquémica

El objetivo de este trabajo es analizar posibles diferencias ecocardiograficas y bioquimicas (NT-proBNP) entre controles y pacientes diabeticos tipo 2 sin cardiopatia isquemica y con ella. El estudio ecocardiografico comprendio la forma y la funcion ventricular izquierda. Ademas se determinaron las concentraciones plasmaticas de NT-proBNP. Los diabeticos sin cardiopatia isquemica presentaron mayor prevalencia de disfuncion diastolica (el 88 frente al 74%; p 490 fmol/ml tuvo el 84% de sensibilidad y el 75% de especificidad para detectar cardiopatia isquemica en pacientes diabeticos.

Recomendaciones sobre las indicaciones clínicas de la gated-SPECT de perfusión miocárdica

Desde 1999 no se habia realizado ninguna revision de las Guias de actuacion clinica de la Sociedad Espanola de Cardiologia en Cardiologia Nuclear, por lo que en este articulo exponemos las indicaciones clase I y IIa de la American College of Cardiology/American Heart Association/American Society of Nuclear Cardiology (ACC/AHA/ASNC) con nivel de evidencia A o B, junto con las 27 indicaciones consideradas adecuadas por el Comite de expertos de la American College of Cardiology Foundation/American Society of Nuclear Cardiology (ACCF/ASNC) y los comentarios que hemos considerado oportuno anadir los firmantes de este articulo.