New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Cuantificación de la extrasistolía supraventricular y ventricular en el holter de 24 horas: significación pronóstica en estudios actuales / Quantification and clinical significance of supraventricular and ventricular extrasystoles in holter recordings: a review

En la actualidad existen diferencias en la interpretación y cuantificación de los extrasístoles supraventriculares y ventriculares en el Holter de ritmo cardíaco y no existe siempre una misma definición e interpretación de lo que se denomina como "escaso", "ocasional", "frecuente" o "muy frecuente". El objetivo del presente trabajo ha sido revisar las evidencias actuales y sus fundamentos en relación a la cuantificación o carga de la extrasistolía supraventricular y ventricular en un Holter de ritmo cardíaco, lo que debiera contribuir a una mayor precisión y mejor interpretación de la información cuantitativa en la práctica clínica diaria con este examen. Se revisa en la literatura el concepto de carga de extrasístoles supraventriculares y ventriculares y su relación con eventos clínicos: fibrilación auricular y accidente cerebrovascular en el caso de la extrasistolía supraventricular y mortalidad post infarto y deterioro de la función ventricular en el caso de la extrasistolía ventricular. De esta manera se cuantifica en base a la evidencia la extrasistolía supraventricular y ventricular.

Considerable differences exist in the quantification and clinical significance of both supraventricular and ventricular extrasystoles found in Holter recordings. Usually extrasystoles were classified as rare, occasional, frequent and very frequent. Current publications were analyzed regarding the frequency and clinical significance or these arrhythmias, especially in in relation to prior myocardial infarction, ventricular dysfunction, atrial fibrillation and cerebro vascular events. Tables showing limits to define the severity of supraventricular and ventricular extrasystoles are included.

Cardiomiopatía amiloídea por transtiretina: diagnóstico y manejo en la actualidad / Transthyretin amyloid cardiomyopathy: a review

RESUMEN: La cardiomiopatía amiloide por transtiretina (CATTR) es una enfermedad caracterizada por depósito extracelular de fibrillas amiloides en el miocardio, a partir de transtiretina mal plegada, generando una miocardiopatía restrictiva. Esta proteína mal plegada puede tener origen hereditario o adquirido, siendo más frecuente en adultos mayores. La CA-TTR ha surgido como una causa subdiagnosticada de insuficiencia cardíaca con fracción de eyección preservada (IC FEp). El pilar fundamental para su diagnóstico es la alta sospecha clínica, basada en diversas banderas de alerta ya que la sintomatología que provoca suele ser inespecífica. Como veremos en esta revisión, el diagnóstico puede sustentarse con la cintigrafía ósea, reservando para situaciones particulares la toma de biopsia. Con el advenimiento de nuevas terapias que impactan en la sobrevida de esta enfermedad, el tiempo para realizar el diagnóstico certero y la diferenciación de otras causas de amiloidosis cardíaca como la de cadenas livianas, se ha tornado crucial.

ABSTRACT: Transthyretin amyloid cardiomyopathy (AT-TR-CM) is a disease characterized by extracellular deposition of amyloid fibrils in the myocardium, from misfolded transthyretin, generating a restrictive cardiomyopathy. This misfolded protein may be inherited or acquired, and is more prevalent in elderly patients. ATTR-CM has emerged as an underdiagnosed cause of heart failure with preserved ejection fraction (HF-PEF). The fundamental pillarfor its diagnosis is high clinical suspicion since the symptoms are usually nonspecific. The diagnosis can be made from bone scintigraphy, reserving myocardial biopsy for particular situations. With the advent of new therapies that affect the survival of these patients, a timely diagnosis has become crucial.

[Cardiotoxicity of anticancer therapies. Towards the implementation of cardio-oncology units]. / Cardiotoxicidad inducida por tratamientos oncológicos. Fundamentos para la implementación de equipos de Cardio-Oncología.

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

Cardiotoxicidad inducida por tratamientos oncológicos: fundamentos para la implementación de equipos de Cardio-Oncología / Cardiotoxicity of anticancer therapies: towards the implementation of cardio-oncology units

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

Relationship between mechanical and metabolic dyssynchrony with left bundle branch block: evaluation by 18-fluorodeoxyglucose positron emission tomography in patients with non-ischemic heart failure.

BACKGROUND: Ventricular dyssynchrony is a common finding in patients with heart failure (HF), especially in the presence of conduction delays. The loss of ventricular synchrony leads to progressive impairment of contractile function, which may be explained in part by segmental abnormalities of myocardial metabolism. However, the association of these metabolic disarrangements with parameters of ventricular dyssynchrony and electrocardiography (ECG) findings has not yet been studied. METHODS: Our aim was to determine the correlation between the presence of left bundle branch block (LBBB) with left ventricular (LV) mechanical synchrony assessed by multiple-gated acquisition scan (MUGA) and with patterns of 18-fluorodeoxyglucose (18FDG) uptake in patients with non-ischemic heart failure. Twenty-two patients with non-ischemic cardiomyopathy, LV ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) Functional Class II or III symptoms under standard medical therapy were included, along with 10 healthy controls matched for age and gender. A 12-lead ECG was obtained to measure the length of the QRS. Mechanical LV synchrony was assessed by MUGA using phase analysis. All patients and controls underwent positron emission tomography with 18FDG to determine the distribution of myocardial glucose uptake. The standard deviation of peak (18)FDG uptake was used as an index of metabolic heterogeneity. Student's t-test and Pearson's correlation were used for statistical analysis. RESULTS: The mean age of the patients with HF was 54 ± 12 years and 72% were male. The length of the QRS was 129 ± 31 milliseconds and LBBB was present in 9 patients. Patients with HF had decreased LV 18FDG uptake compared with controls (7.56 ± 3.36 vs. 11.63 ± 4.55 standard uptake value; p = 0.03). The length of the QRS interval correlated significantly with glucose uptake heterogeneity (r = 0.62; p = 0.002) and mechanical dyssynchrony (r = 0.63; p = 0.006). HF patients with LBBB showed marked glucose uptake heterogeneity compared with HF patients without LBBB (41.4 ± 10 vs 34.7 ± 4.9 ml/100 g/min, respectively; p = 0.01). CONCLUSIONS: Patients with non-ischemic heart failure exhibit a global decrease in myocardial glucose uptake. Within this group, subjects who also have LBBB exhibit a marked heterogeneity in segmental glucose uptake, which directly correlates with QRS duration.

Systemic oxidative stress and endothelial dysfunction is associated with an attenuated acute vascular response to inhaled prostanoid in pulmonary artery hypertension patients.

BACKGROUND: Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary arterial hypertension (PAH). We evaluate whether oxidative stress and endothelial dysfunction are associated with acute pulmonary vascular bed response to an inhaled prostanoid in PAH patients. METHODS: Fourteen idiopathic PAH patients and 14 controls were included. Oxidative stress was assessed through plasma malondialdehyde (MDA) levels and xanthine oxidase (XO) and endothelial-bound superoxide dismutase (eSOD) activity. Brachial artery endothelial-dependent flow-mediated vasodilation (FMD) was used to evaluate endothelial function. Hemodynamic response to inhaled iloprost was assessed with transthoracic echocardiography. RESULTS: PAH patients showed impaired FMD (2.8 ± 0.6 vs. 10.7 ± 0.6%, P < .01), increased MDA levels and XO activity (0.6 ± 0.2 vs. 0.3 ± 0.2 µM, P < .01 and 0.04 ± 0.01 vs. 0.03 ± 0.01 U/mL, P = .02, respectively) and decreased eSOD activity (235 ± 23 vs. 461 ± 33 AUC, P < .01). Iloprost improved right cardiac output (3.7 ± 0.6 to 4.1 ± 1.2 L/min, P = .02) and decreased pulmonary vascular resistance (4.1 ± 1.1 to 2.9 ± 0.9 Wood U, P = .01). Changes in right cardiac output after prostanoid inhalation correlated significantly with baseline eSOD activity and FMD (Rho: 0.61, P < .01 and Rho: 0.63, P = .01, respectively). CONCLUSION: PAH patients show increased systemic oxidative stress and endothelial dysfunction markers. Response to inhaled prostanoid is inversely related to both parameters.

[Changes long term prognosis of 17 patients with pulmonary artery hypertension]. / Cambios en el pronóstico a largo plazo de la hipertensión arterial pulmonar.

BACKGROUND: Pulmonary artery hypertension (PAH) is a progressive disease with high mortality. Major advances had been made in the treatment of this condition during the last decade. AIM: To characterize the clinical evolution and mortality of a cohort of Chilean patients. MATERIAL AND METHODS: Seventeen patients with PAH diagnosed in the last 10 years in two Chilean hospitals were enrolled. Measurements at diagnosis included hemodynamic variables and 6-minute walk test. The patients were followed clinically for 3 years and the observed mortality was compared with that predicted by the prognostic equation proposed by the historic registry of the National Institutes of Health (NIH). RESULTS: The mean age of patients was 45 years and 80% had an idiopathic PAH. The mean median pulmonary artery pressure was 57 ± 15 mmHg, the cardiac index was 2.4 ± 0.7 l/min/m² and the right atrial pressure was 12 ± 8 mmHg. The 6-minute walk distance was 348 ± 98 m. All patients received anticoagulants. Eighty two percent received ambrisentan, 12% received bosentan, 29% received iloprost and 24% sildenafil. At the end of follow-up only 3 patients had died, with an observed survival rate of 88, 82 and 82% at 1, 2 and 3 years, respectively. In contrast, the survival calculated according to the predictive formula of the NIH was 67, 56 and 45%, respectively. Among surviving patients, an improvement in exercise capacity was observed after one year (p < 0.05). CONCLUSIONS: The observed survival rate was significantly better than that estimated according to historical data. Furthermore, therapy was associated with an improvement in functional capacity after one year. This prognostic improvement is consistent with data of other contemporary registries published after the NIH Registry.

[The role of uric acid in heart failure]. / Ácido úrico: una molécula con acciones paradójicas en la insuficiencia cardiaca.

Complications and mortality of heart failure are high, despite the availability of several forms of treatment. Uric acid, the end product of purine metabolism would actively participate in the pathophysiology of heart failure. However, there is no consensus about its action in cardiovascular disease. Serum uric acid would have a protective antioxidant activity. This action could help to reduce or counteract the processes that cause or appear as a result of heart failure. However, these protective properties would vanish in the intracellular environment or in highly hydrophobic areas such as atherosclerotic plaques and adipose tissue. This review discusses the paradoxical action of uric acid in the pathophysiology of heart failure.

Ácido úrico: una molécula con acciones paradójicas en la insuficiencia cardiaca / The role of uric acid in heart failure

Complications and mortality of heart failure are high, despite the availability of several forms of treatment. Uric acid, the end product of purine metabolism would actively participate in the pathophysiology of heart failure. However, there is no consensus about its action in cardiovascular disease. Serum uric acid would have a protective antioxidant activity. This action could help to reduce or counteract the processes that cause or appear as a result of heart failure. However, these protective properties would vanish in the intracellular environment or in highly hydrophobic areas such as atherosclerotic plaques and adipose tissue. This review discusses the paradoxical action of uric acid in the pathophysiology of heart failure.

Cambios en el pronóstico a largo plazo de la hipertensión arterial pulmonar / Changes long term prognosis of 17 patients with pulmonary artery hypertension

Background: Pulmonary artery hypertension (PAH) is a progressive disease with high mortality. Major advances had been made in the treatment of this condition during the last decade. Aim: To characterize the clinical evolution and mortality of a cohort of Chilean patients. Material and Methods: Seventeen patients with PAH diagnosed in the last 10 years in two Chilean hospitals were enrolled. Measurements at diagnosis included hemodynamic variables and 6-minute walk test. The patients were followed clinically for 3 years and the observed mortality was compared with that predicted by the prognostic equation proposed by the historic registry of the National Institutes of Health (NIH). Results: The mean age of patients was 45 years and 80 percent had an idiopathic PAH. The mean median pulmonary artery pressure was 57 ± 15 mmHg, the cardiac index was 2.4 ± 0.7 l/min/m² and the right atrial pressure was 12 ± 8 mmHg. The 6-minute walk distance was 348 ± 98 m. All patients received anticoagulants. Eighty two percent received ambrisentan, 12 percent received bosentan, 29 percent received iloprost and 24 percent sildenafil. At the end of follow-up only 3 patients had died, with an observed survival rate of88, 82 and 82 percent at 1, 2 and 3 years, respectively. In contrast, the survival calculated according to the predictive formula of the NIH was 67, 56 and 45 percent, respectively. Among surviving patients, an improvement in exercise capacity was observed after one year (p < 0.05). Conclusions: The observed survival rate was significantly better than that estimated according to historical data. Furthermore, therapy was associated with an improvement in functional capacity after one year. This prognostic improvement is consistent with data of other contemporary registries published after the NIH Registry.

Xanthine-oxidase inhibitors and statins in chronic heart failure: effects on vascular and functional parameters.

BACKGROUND: Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed. METHODS: This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) <40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATV+PLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATV+ALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT). RESULTS: Thirty-two patients were randomized to ATV+PLA and 38 to ATV+ALLO. Mean age was 59 ± 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.5 to 0.9 ± 0.1 µmol/liter, p = 0.88), UA (7.4 ± 0.4 to 6.8 ± 0.3 and 7.2 ± 0.4 to 5.0 ± 0.3 mg/dl, p < 0.01) and FDD (3.9 ± 0.2% to 5.6 ± 0.4% and 4.6 ± 0.3% to 7.1 ± 0.5%, p = 0.07) with increased ecSOD activity (109 ± 11 to 173 ± 13 and 98 ± 10 to 202 ± 16, U/ml/min, p = 0.41) and improved 6MWT (447 ± 18 to 487 ± 19 and 438 ± 17 to 481 ± 21 m, p = 0.83), with all values for ATV+PLA and ATV+ALLO, respectively; p-values are for comparison between groups after treatment. CONCLUSION: Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strengthened by the addition of allopurinol.

[Heart energy metabolism and its role in the treatment of heart failure]. / Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca.

It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

Determinaciones de niveles de creatina y lípidos mediante espectroscopia por resonancia magnética en miocardio de pacientes con insuficiencia cardiaca no isquémica / Myocardial lipids and creatine measured by magnetic resonance spectroscopy among patients with heart failure

Background: Heart failure (HF) is characterized, among other features, by the development of alterations in myocardial energy metabolism, involving a decrease in glucose utilization and increased free fatty acid uptake by cardiomyocytes, associated with decreased deposits of high-energy phosphates (creatine phosphate/ creatine transporter). Magnetic resonance (MR) imaging allows a direct and noninvasive assessment of myocardial metabolites. Aim: To measure myocardial creatine and lipids by MR spectroscopy among patients with HF. Material and Methods: Cardiac MR spectroscopy (1.5 Tesla) with Hydrogen antenna and single voxel acquisition was performed in fve patients with non-ischemic heart failure, aged 58 ± 9.7 years, (60 percent males) and 5 healthy volunteers matched for age and sex. We analyzed the signals of creatine (Cr), lipids (L) and water (W) in the interventricular septum, establishing the water/lipid (W/L) and water/creatine (W/Cr) index to normalize the values obtained. Results: Among patients, left ventricular ejection fraction was 32 ± 6.9 percent, 60 percent were in functional capacity II, 60 percent had hypertension and one was diabetic. Spectroscopic curves showed a depletion of total Cr, evidenced by the W/ Cr index, among patients with heart failure, when compared with healthy controls (1.46 ± 1.21 and 5.96 ± 2.25 respectively, p < 0,05). Differences in myocardial lipid content, measured as the W/L index, were not significant (5.06 ± 2.66 and 1.80 ± 1.62 respectively, p = 0.08). Conclusions: Among patients with heart failure of non-ischemic etiology, there is a depletion of creatine levels measured by MR spectroscopy.

Implicancias de la glicemia de ingreso en la mortalidad intrahospitalaria y alejada según el método de reperfusión en pacientes con infarto agudo del miocardio y supradesnivel del segmento ST / Admission hyperglycemia and mortality of ST segment elevation myocardial infarction

Background: Hyperglycemia at admission has been associated to an adverse prognosis in patients with ST-segment elevation acute myocardial infarction (STE-MI). However, its impact over the results of reperfusion therapies in patients with STEMI is still a matter of controversy. Aim: To determine the impact of admission hyperglycemia on hospital and long term mortality, according to the method of reper-fusion utilized in patients with STEMI. Material and Methods: Prospective registry of 1,634 consecutive patients aged 60 ± 12 years (77 percent male), from 3 participating hospitals in the Chilean Registry of Myocardial Infarction (GEMI). We evaluated demographic, clinical and laboratory variables, reperfusion method used, hospital and long term mortality. The impact of hyperglycemia on hospital and long term mortality was evaluated by a logistic regression analysis and Cox risk, respectively, adjusted by Thrombolysis in Myocardial Infarction (TIMI) risk score. Results: Twenty four percent of patients were diabetics and in 45 percent, the infarct was located on the anterior wall. The mean TIMI risk score was 3.2 ± 2.4. Hyperglycemia at entry was associated to a greater hospital and long term mortality, independently of the reperfusion strategy utilized. Primary angioplasty was associated to a greater benefit, compared to thrombolysis among hyperglycemic patients with an odds ratio: 2.9, 95 percent confi dence intervals: 1.0-8.0 and a hazard ratio of 2.9, 95 percent confi dence intervals: 1.44-5.88, independently of a previous history of diabetes mellitus and TIMI risk score. Conclusions: In patients with STEMI, admission hyperglycemia is associated with a worse prognosis which was significantly improved with primary angioplasty compared to thrombolysis, independently of the admission TIMI risk score.

Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca / Heart energy metabolism and its role in the treatment of heart failure

It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

[Myocardial lipids and creatine measured by magnetic resonance spectroscopy among patients with heart failure]. / Determinaciones de niveles de creatina y lípidos mediante espectroscopia por resonancia magnética en miocardio de pacientes con insuficiencia cardiaca no isquémica.

BACKGROUND: Heart failure (HF) is characterized, among other features, by the development of alterations in myocardial energy metabolism, involving a decrease in glucose utilization and increased free fatty acid uptake by cardiomyocytes, associated with decreased deposits of high-energy phosphates (creatine phosphate/creatine transporter). Magnetic resonance (MR) imaging allows a direct and noninvasive assessment of myocardial metabolites. AIM: To measure myocardial creatine and lipids by MR spectroscopy among patients with HF. MATERIAL AND METHODS: Cardiac MR spectroscopy (1.5 Tesla) with Hydrogen antenna and single voxel acquisition was performed in five patients with non-ischemic heart failure, aged 58 ± 9.7 years, (60% males) and 5 healthy volunteers matched for age and sex. We analyzed the signals of creatine (Cr), lipids (L) and water (W) in the interventricular septum, establishing the water/lipid (W/L) and water/creatine (W/Cr) index to normalize the values obtained. RESULTS: Among patients, left ventricular ejection fraction was 32 ± 6.9%, 60% were in functional capacity II, 60% had hypertension and one was diabetic. Spectroscopic curves showed a depletion of total Cr, evidenced by the W/ Cr index, among patients with heart failure, when compared with healthy controls (1.46 ± 1.21 and 5.96 ± 2.25 respectively, p < 0,05). Differences in myocardial lipid content, measured as the W/L index, were not significant (5.06 ± 2.66 and 1.80 ± 1.62 respectively, p = 0.08). CONCLUSIONS: Among patients with heart failure of non-ischemic etiology, there is a depletion of creatine levels measured by MR spectroscopy.

[Admission hyperglycemia and mortality of ST segment elevation myocardial infarction]. / Implicancias de la glicemia de ingreso en la mortalidad intrahospitalaria y alejada según el método de reperfusión en pacientes con infarto agudo del miocardio y supradesnivel del segmento ST.

BACKGROUND: hyperglycemia at admission has been associated to an adverse prognosis in patients with ST-segment elevation acute myocardial infarction (STE-MI). However, its impact over the results of reperfusion therapies in patients with STEMI is still a matter of controversy. AIM: to determine the impact of admission hyperglycemia on hospital and long term mortality, according to the method of reper-fusion utilized in patients with STEMI. MATERIAL AND METHODS: prospective registry of 1,634 consecutive patients aged 60 ± 12 years (77% male), from 3 participating hospitals in the Chilean Registry of Myocardial Infarction (GEMI). We evaluated demographic, clinical and laboratory variables, reperfusion method used, hospital and long term mortality. The impact of hyperglycemia on hospital and long term mortality was evaluated by a logistic regression analysis and Cox risk, respectively, adjusted by Thrombolysis in Myocardial Infarction (TIMI) risk score. RESULTS: twenty four percent of patients were diabetics and in 45%, the infarct was located on the anterior wall. The mean TIMI risk score was 3.2 ± 2.4. Hyperglycemia at entry was associated to a greater hospital and long term mortality, independently of the reperfusion strategy utilized. Primary angioplasty was associated to a greater benefit, compared to thrombolysis among hyperglycemic patients with an odds ratio: 2.9, 95% confi dence intervals: 1.0-8.0 and a hazard ratio of 2.9, 95% confi dence intervals: 1.44-5.88, independently of a previous history of diabetes mellitus and TIMI risk score. CONCLUSIONS: in patients with STEMI, admission hyperglycemia is associated with a worse prognosis which was significantly improved with primary angioplasty compared to thrombolysis, independently of the admission TIMI risk score.

Niveles aumentados de estrés oxidativo se asocian a disfunción endotelial periférica y respuesta vascular pulmonar disminuida frente a vasodilatadores en pacientes con hipertensión pulmonar / Increased oxidative stress are associated with peripheral endothelial dysfunction and diminished vascular response to vasodilators in pulmonary hypertensive patients

Introducción: La Hipertensión arterial pulmonar (HP) se caracteriza por remodelado vascular y disfunción endotelial. Evidencia experimental muestra que el estrés oxidativo juega un rol importante en la patogénesis de la HP. El rol del estrés oxidativo, su relación con la función endotelial periférica y con la respuesta vascular pulmonar a vasodilatadores en pacientes con HP no está aclarada. Objetivo: evaluar parámetros de estrés oxidativo y función endotelial periférica en pacientes con HP y estudiar su relación con la respuesta vascular pulmonar frente a vasodilatadores. Métodos: estudio transversal. Se incluyeron 14 pacientes con HP y 14 controles pareados por edad y sexo. En todos los sujetos se midieron: niveles plasmáticos de malondialdehido (MDA), superóxido dismutasa ligada a endotelio (eSOD) y xantino oxidasa (eXO). Vasodilatación dependiente de endotelio mediada por flujo en arteria braquial fue usada como marcador de función endotelial (FDD). Función ventricular derecha y reactividad del lecho vascular pulmonar frente a iloprost inhalado fueron evaluadas ecocardiográficamente en los pacientes con HP Resultados: Los pacientes con HP presentaron FDD disminuida versus los controles (2,8 +/- 0,6 vs 10,7 por ciento +/- 0,6, p< 0,01). Niveles de MDA y eXO aumentados (0,61 +/- 0,17 vs 0,34 +/- 0,15uM, p<0,01 y 0,039 +/- 0,005 vs 0,034 +/- 0,004 U/mL1, p=0,02 respectivamente) y actividad de eSOD disminuida (235,55 +/- 23 vs 461,41 +/- 33 ABC, p<0,01). Iloprost mejora significativamente el gasto cardíaco derecho y disminuye la resistencia vascular pulmonar en los pacientes con HP y este cambio se correlaciona con la actividad de eSOD (Rho: 0,61, p<0,01) y FDD (Rho: 0,63, p=0,01). Conclusiones: Pacientes con HP presentan parámetros de estrés oxidativo elevados y disfunción endotelial periférica La respuesta hemodinámica frente al uso de Iloprost se correlaciona con estos parámetros sugiriendo un rol en la HP cuyo valor clínico deberá ser evaluado.

Background: Pulmonary Arterial Hypertension (PAH) is characterized by endothelial dysfunction and vascular remodeling. Several lines of experimental evidence indicate that oxidative stress plays an important role in the pathogenesis of PAH. The role of oxidative stress and its relation with peripheral endothelial function and pulmonary vascular response to vasodilators remains unknown. Aim: To evaluate whether systemic oxidative stress and endothelial dysfunction markers are associated with the response of the pulmonary vascular bed to inhaled vasodilators in PAH patients. Methods: Cross-sectional study Fourteen patients with PAH and 14 age and gender-matched controls were included. Systemic oxidative stress was assessed through plasma malondialdehyde (MDA), xanthine oxidase (eXO) levels and endothelial-bound superoxide dismutase (eSOD) activity Brachial artery endothelial-de-pendent flow-mediated vasodilation (FDD) was used to evaluate endothelial function. Right ventricular function and pulmonary vascular bed reactivity to inhaled vasodilators was determined with echocardiography in PAH patients. Results: Compared to controls, PAH patients showed impaired FDD (2.8 +/- 0.6 vs 10.7 percent +/- 0.6, p< 0.01), increased MDA and eXO levels (0.61 +/- 0.17 vs 0.34 +/- 0.15uM, p<0.01 and 0.039 +/- 0.005 vs 0.034 +/- 0.004 U/ mL1, p=0.02 , respectively) and decreased eSOD activity 235.55 +/- 23 vs 461.41 +/- 33 AUC, p<0.01). Iloprost significantly improved right cardiac output (RCO) and decreased pulmonary vascular resistance. The amount of change in RCO after iloprost inhalation correlated significantly with baseline eSOD activity and FDD (Rho: 0.61, p<0.01 and Rho: 0.63, p=0.01 respectively). Conclusions: PAH patients show increased oxidative stress and endothelial dysfunction markers. Response to inhaled iloprost is closely related with baseline endothelial function and oxidative stress parameters, suggesting an important role of these elements that re...