María Luaces

Leptin induces cardiac fibrosis through galectin-3, mtor and oxidative stress: potential role in obesity

Objective: Leptin acts as a cardiac profibrotic factor. However, the mechanisms underlying this effect are unclear. Therefore, we sought to elucidate the mediators involved in this process and the potential role of leptin in cardiac fibrosis associated with obesity. Methods: Male Wistar rats were fed either a high-fat diet (HFD; 33.5% fat), or a standard diet (3.5% fat) for 6 weeks. Results: HFD animals show cardiac hypertrophy, fibrosis and an increase in O2- production as evaluated by dihydroethidium. Echocardiographic parameters of cardiac structure and systolic function were similar in both groups. Cardiac levels of leptin, collagen I, galectin-3 and transforming growth factor &bgr; (TGF-&bgr;) were higher in HFD than in controls. In cardiac myofibroblasts, leptin (10–100 ng/ml) increased O2−, collagen I, galectin-3, TGF-&bgr; and connective tissue growth factor production (CTGF). These effects were prevented by the presence of either melatonin (10−3 mmol/l) or the inhibitor of mTOR, rapamycin (10−4 mmol/l). Blockage of galectin-3 activity by N-acetyllactosamine (LacNac 10−3 mmol/l) reduced both collagen I and O2.− production induced by leptin. The p70S6 kinase activation/phosphorylation, the downstream mediator of mTOR, induced by leptin was not modified by melatonin. Leptin reduced the metalloproteinase (MMP) 2 activity and the presence of melatonin, rapamycin or LacNac were unable to prevent it. Conclusion: The data suggest that leptin locally produced in the heart could participate in the fibrosis observed in HFD by affecting collagen turnover. Collagen synthesis induced by leptin seems to be mediated by the production of galectin-3, TGF-&bgr; and CTGF through oxidative stress increased by activation of mTOR pathway.

Modificaciones anatomofuncionales del corazón en la obesidad mórbida. Cambios tras la cirugía bariátrica

INTRODUCTION AND OBJECTIVES Cardiac adaptation to obesity includes both structural and functional changes in the heart. The therapeutic option of last resort for morbidly obese patients is bariatric surgery. This study aims to assess the anatomical functional changes in the heart for a Spanish cohort of morbidly obese patients, as well as changes after bariatric surgery. METHODS Patients referred for bariatric surgery were prospectively included. In each case, a transthoracic echocardiography, electrocardiogram, and blood tests were performed before the procedure and repeated 1 year after surgery. RESULTS Forty-one patients completed the 1-year follow-up. Of these, 82.9% were female. Mean age was 40.2±9.6 years. Prior to surgery, mean body mass index was 47.41 kg/m(2), decreasing to 30.43 kg/m(2) after the procedure. Before surgery, cardiac remodeling was present in 70.7%, most frequently in the form of eccentric hypertrophy (34.1%). At 1-year follow-up, 58.5% showed a normal left ventricular geometric pattern (P=.02). Mitral inflow E/A ratio changed from 1.14 to 1.43 (P<.001). Nevertheless, early mitral velocity measured by Doppler tissue decreased (P=.06). CONCLUSIONS In morbidly obese patients referred for bariatric surgery, cardiac remodeling is highly prevalent, in most cases in an eccentric manner. Weight loss achieved by bariatric surgery is accompanied by significant improvements in left ventricular structure. Nevertheless, the damage in diastolic function may be permanent despite weight loss.

Proximal Isovelocity Surface Area by Single-Beat Three-Dimensional Color Doppler Echocardiography Applied for Tricuspid Regurgitation Quantification

BACKGROUND The two-dimensional (2D) proximal isovelocity surface area (PISA) method has known technical limitations, mainly the geometric assumptions of PISA shape required to calculate effective regurgitant orifice area (EROA). Recently developed single-beat real-time three-dimensional (3D) color Doppler imaging allows the direct measurement of PISA without geometric assumptions and has already been validated for mitral regurgitation assessment. The aim of this study was to apply this novel method in patients with chronic tricuspid regurgitation (TR). METHODS Ninety patients with chronic TR were enrolled. EROA and regurgitant volume (Rvol) were assessed using transthoracic 2D and 3D PISA methods. Quantitative Doppler and 3D transthoracic planimetry of EROA were used as reference methods. RESULTS Both EROA and Rvol assessed using the 3D PISA method had better correlations with the reference methods than using conventional 2D PISA, particularly in the assessment of eccentric jets. On the basis of 3D planimetry-derived EROA, 35 patients had severe TR (EROA ≥ 0.4 cm(2)). Among these 35 patients, 25.7% (n = 9) were underestimated as having nonsevere TR (EROA ≤ 0.4 cm(2)) using the 2D PISA method. In contrast, the 3D PISA method had 94.3% agreement (33 of 35) with 3D planimetry in classifying severe TR. Good intraobserver and interobserver agreement for 3D PISA measurements was observed, with intraclass correlation coefficients of 0.92 and 0.88 respectively. CONCLUSIONS TR quantification using PISA by single-beat real-time 3D color Doppler echocardiography is feasible in the clinical setting and more accurate than the conventional 2D PISA method.

Electrocardiographic criteria in Takotsubo cardiomyopathy and race differences: Asians versus Caucasians.

Recently, Kosuge et al. ([1][1]) reported an interesting set of electrocardiographic criteria in order to differentiate Takotsubo cardiomyopathy (TC) from anterior myocardial infarction (AMI), with its consequent prognostic implications. ST-segment depression in aVR together with the absence of ST-

Clinical and prognostic comparison between left ventricular transient dyskinesia and a first non-ST-segment elevation acute coronary syndrome.

ObjectivesApical ballooning shares features with acute coronary syndromes. Recently, atypical forms have been reported without apical involvement. Usually, the prognostic reports have compared them with ST-segment elevation infarction. Left ventricular transient dyskinesias (LVTD), however, frequently occur without ST-segment elevation and when present, these patients always have open arteries. Our aim was to assess the baseline features, clinical presentation, natural history and compare long-term prognosis in an LVTD-cohort with a first non-ST-segment elevation acute coronary syndrome (NSTEMI) group. MethodsWe performed a prospective observational study including consecutive patients in two groups: (i) LVTD group: 62 patients with this syndrome between 2003 and 2007. Inclusion criteria were LV segmental transient motion abnormalities; ECG new alterations and elevated troponin; absence of recent significant head trauma or obstructive coronary artery lesions. (ii) Control group: 169 patients admitted for a first NSTEMI in 2004. ResultsMedian follow-up was 35 months. Mean age was 65 years. LVTD group included 83.9% females. NSTEMI group was predominantly males. Eleven in-hospital deaths happened in NSTEMI cohort and none in LVTD. Four patients in the LVTD group required readmission and two patients died. In the NSTEMI group, heart failure, unstable angina, myocardial infarction (P<0.001) and death (P=0.11) were more frequent. Cox regression showed that diabetes mellitus, significant onset mitral regurgitation and NSTEMI versus LVTD were found as event-independent predictors. ConclusionLVTD diagnosis represents a decreased risk of events when compared with classic non-ST-segment acute coronary syndrome, pointing out a different pathophysiologic mechanism.

Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity

Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity.

Quantification of left atrial volumes using three-dimensional wall motion tracking echocardiographic technology: comparison with cardiac magnetic resonance

BACKGROUND Left atrium (LA) size assessment is clinically relevant, but the accuracy of two-dimensional echocardiographic (2D-echo) methods is limited. Three-dimensional (3D) echocardiography is an excellent alternative but is far from being used in daily clinical practice. Three-dimensional-wall motion tracking (3D-WMT) allows us to obtain volumes in a very simple and rapid manner. The aims of this study were to evaluate the accuracy of 3D-WMT technology to assess LA volume using cardiac magnetic resonance (CMR) as a reference method, to evaluate its reproducibility, and to determine its added clinical value to classify the LA enlargement severity. METHODS AND RESULTS Seventy consecutive patients referred for a CMR study were prospectively enrolled. They underwent LA volume assessment by means of 2D-echo, 3D-WMT, and CMR. Inter-methods agreement was assessed. The mean age was 56 ± 18 years and 42 patients (60%) were males. Average maximal LA volume obtained by 2D-echo, 3D-WMT, and CMR were 63.33 ± 26.82, 79.80 ± 29.0, and 79.80 ± 28.99 mL, respectively. Univariate linear regression analysis showed a good correlation between 3D-WMT and CMR (r = 0.83; P < 0.001). The agreement analysis showed a similar result (ICC = 0.83; 95% CI = 0.74-0.89; P < 0.001). Furthermore, the LA enlargement degree was better evaluated with 3D-WMT than with 2D-echo. CONCLUSION This study validates LA volume measurements obtained using the new and fast 3D-WMT technology, compared with CMR. This method is fast, accurate, and reproducible, and it allows a better classification of left LA enlargement severity compared with 2D-echo.

Vegetation size at diagnosis in infective endocarditis: influencing factors and prognostic implications.

The role of vegetation as the key feature of infective endocarditis is universally recognized. Nowadays, the wide availability of transesophageal echocardiography has made of it the most employed technique to establish the diagnosis by visualizing vegetations. However, the factors which influence the size of vegetation when first detected are not clearly determined. Furthermore, there is considerable controversy regarding the prognostic implications of the size of vegetation. This is of paramount significance to early identify patients at high risk for complications, which might benefit from aggressive attitudes. We present a study based on TEE. Our results show that the size of vegetation at admission is mostly determined by anatomical and not microbiological factors, and the prognostic influence of vegetations on the risk of embolisms, need of surgery, persistent infection and septic shock.

The lysyl oxidase inhibitor (β-aminopropionitrile) reduces leptin profibrotic effects and ameliorates cardiovascular remodeling in diet-induced obesity in rats

Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling. We explore the impact of LOX inhibition in ECM alterations induced by obesity in the cardiovascular system. LOX is overexpressed in the heart and aorta from rats fed a high-fat diet (HFD). β-Aminopropionitrile (BAPN), an inhibitor of LOX activity, significantly attenuated the increase in body weight and cardiac hypertrophy observed in HFD rats. No significant differences were found in cardiac function or blood pressure among any group. However, HFD rats showed cardiac and vascular fibrosis and enhanced levels of superoxide anion (O2(-)), collagen I and transforming growth factor β (TGF-β) in heart and aorta and connective tissue growth factor (CTGF) in aorta, effects that were attenuated by LOX inhibition. Interestingly, BAPN also prevented the increase in circulating leptin levels detected in HFD fed animals. Leptin increased protein levels of collagen I, TGF-β and CTGF, Akt phosphorylation and O2(-) production in both cardiac myofibroblasts and vascular smooth muscle cells in culture, while LOX inhibition ameliorated these alterations. LOX knockdown also attenuated leptin-induced collagen I production in cardiovascular cells. Our findings indicate that LOX inhibition attenuates the fibrosis and the oxidative stress induced by a HFD on the cardiovascular system. The reduction of leptin levels by BAPN in vivo and the ability of this compound to inhibit leptin-induced profibrotic mediators and ROS production in cardiac and vascular cells suggest that interactions between leptin and LOX regulate downstream events responsible for myocardial and vascular fibrosis in obesity.

Perfil actual de la endocarditis por estafilococo coagulasa negativo en válvulas nativas izquierdas

Los estafilococos coagulasa negativos (SCN) son los microorganismos aislados con mas frecuencia en la endocarditis protesica temprana. En cambio, afectan en pocas ocasiones a las valvulas nativas. Hay escasos y antiguos datos en la bibliografia sobre la endocarditis nativa izquierda por SCN, por lo que su perfil es poco conocido. Hemos analizado las caracteristicas epidemiologicas, clinicas, radiologicas, microbiologicas, ecocardiograficas y evolutivas de 17 casos de endocarditis izquierda nativa por SCN obtenidas de una serie de 441 episodios consecutivos de endocarditis. Los resultados muestran un aumento en la frecuencia de esta enfermedad respecto de las series previas. Clinicamente provocan en numerosas ocasiones insuficiencia cardiaca por afeccion valvular, precisan con frecuencia cirugia y tienen una alta mortalidad.