Luigi Gabrielli

Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity.

BACKGROUND Increased oxidative stress, a common feature in chronic heart failure, has been associated with inflammation, endothelial dysfunction, and extracellular matrix degradation. Statins have known anti-inflammatory and anti-oxidant effects; however, their role in chronic heart failure is still controversial. METHODS This was a prospective study of 38 patients with stable systolic chronic heart failure. Patients received a 4-week placebo course, followed by atorvastatin 20 mg/day for 8 weeks. Oxidative stress, inflammation and remodeling markers, brachial artery flow-mediated vasodilation, and 6-minute walk test were evaluated at baseline, 4, and 8 weeks. RESULTS Mean age was 58 +/- 12. Mean left ventricular ejection fraction was 27% +/- 12%. No significant differences were observed between measurements at baseline and after placebo. Atorvastatin induced a significant decrease of matrix metalloproteinase-9 activity, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and malondialdehyde, and a significant increase of endothelial superoxide dismutase activity when compared with placebo. No differences in tissue inhibitor of matrix metalloproteinase and matrix metalloproteinase-2 activities were observed. Atorvastatin use was associated with an improved flow-dependent brachial vasodilation and exercise capacity in the 6-minute walk test. CONCLUSIONS In chronic heart failure patients, atorvastatin therapy is associated with a decrease of inflammation and extracellular matrix remodeling, improving both endothelial function and exercise capacity.

Assessment of Left Atrial Function in Hypertrophic Cardiomyopathy and Athlete's Heart: A Left Atrial Myocardial Deformation Study

Background: Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death in athletes and differentiating this condition from the nonpathological “athletes heart” remains a challenge. The development of pathological left ventricular hypertrophy (LVH) is associated with left atrial (LA) dilatation and dysfunction. LA strain and strain rate by two‐dimensional (2D) speckle tracking are novel indices of LA function and might contribute to differentiate physiological from pathological LVH among athletes with underdiagnosed HCM. Methods: We evaluated 20 patients with nonobstructive HCM, 20 highly trained athletes and 20 healthy controls matched for age, gender, and body surface area. All patients underwent a transthoracic echocardiogram with evaluation of LA strain: s‐wave (LASs); and strain rate: s‐wave (LASRs) and a‐wave (LASRa). Results: LV mass index, LA volume index, and ejection fraction were comparable between patients with HCM and athletes. Patients with HCM had a significantly lower LASs (19 + 8% vs. 43 + 8%, P < 0.01), LASRs (0.7 + 0.2 s‐1 vs. 1.6 + 0.2 s‐1, P < 0.01), and LASRa (–0.8 + 0.1 s‐1 vs. –1.4 + 0.3 s‐1, P < 0.01) compared to athletes. Among hypertrophic subjects, independent predictors of hypertrophy related to HCM were LASs and E/é ratio. Conclusions: LA myocardial deformation is significantly impaired in patients with HCM compared to athletes and healthy controls. LA strain and strain rate assessed by 2D speckle tracking should be incorporated in the evaluation of trained athletes with LVH and LA dilatation.

Left atrial size and function by three-dimensional echocardiography to predict arrhythmia recurrence after first and repeated ablation of atrial fibrillation

AIMS Left atrial (LA) size has been related to the success of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, potential predictors after a repeated procedure are unknown. We evaluate predictive factors related to successful AF ablation after a first and a repeated RFCA. METHODS AND RESULTS A total of 154 patients with AF were treated with RFCA. LA size and function were assessed with three-dimensional echocardiography (3D Echo) before RFCA. The effectiveness of RFCA was evaluated after 6 months. Recurrence of the arrhythmia was defined as any documented (clinically or by 24-h Holter recording) atrial tachyarrhythmia lasting >30 s after 12 weeks following RFCA. Of 154 patients, 103 (67%) underwent a first ablation (Group 1) and 51 (33%) a repeated RFCA (Group 2). At follow-up, arrhythmias were eliminated in 56 of 103 (54%) patients after a first RFCA and in 20 of 51 (40%) after a repeated ablation. In Group I, hypertension and LA expansion index derived from 3D Echo were independent predictors of arrhythmia elimination. In Group 2, only age predicted persistence of sinus rhythm; and only in younger patients (≤54 year old), though 3D LA maximal volumes were significantly smaller in those without when compared with those with AF recurrences. CONCLUSION A combination of the analysis of LA function with 3D Echo and clinical data predicts elimination of AF after a first ablation procedure for AF, beyond LA size. Among patients undergoing a repeated procedure, age and 3D echocardiographic LA maximum volume in younger patients predict the success of RFCA.

Left atrial deformation predicts success of first and second percutaneous atrial fibrillation ablation.

BACKGROUND Predictors of second radiofrequency catheter ablation (RFCA) success are not well known. Surgical ablation is accepted for failed first RFCA, but second RFCA has fewer complications. OBJECTIVE The purpose of this study was to evaluate left atrial (LA) size and function as potential predictors of second RFCA for atrial fibrillation (AF). METHODS Thirty-three healthy volunteers (group I) and 83 patients with symptomatic drug-refractory AF treated with a first RFCA (group II, n = 48) or a second RFCA (group III, n = 35 patients) were included. Echocardiography was performed in all patients in sinus rhythm before RFCA and in all volunteers. LA size and function were measured using longitudinal strain and strain rate during ventricular systole (LASs, LASRs) and during early diastole (LASRe) or late diastole (LASRa) with speckle tracking echocardiography. The effectiveness of RFCA on arrhythmia recurrence was evaluated at 6-month follow-up. RESULTS LASs, LASRs, and LASRa were significantly lower in group III patients compared to other groups (P < .001 for all). LA diameter or volumes did not predict success after RFCA. LASs was an independent predictor of arrhythmia suppression after a first RFCA and after a second RFCA, with the best cutoff at LASs >20% (sensitivity 86%, specificity 70%) and LASs >12% (sensitivity 84%, specificity 90%), respectively. CONCLUSION LA myocardial deformation imaging is a reliable tool for predicting success after a first and a second RFCA. These parameters could improve candidate selection, especially for a second RFCA.

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.

Markedly increased Rho-kinase activity in circulating leukocytes in patients with chronic heart failure

BACKGROUND The small guanosine triphosphatase Rho and its target Rho-kinase have significant roles in experimental remodeling and ventricular dysfunction, but no data are available on Rho-kinase activation in patients with heart failure (HF). We hypothesized that, in patients with chronic HF, Rho-kinase in circulating leukocytes is activated and related to left ventricular (LV) remodeling and dysfunction. METHODS Accordingly, Rho-kinase activity, assessed by the levels of phosphorylated to total myosin light chain phosphatase 1 (MYPT1-P/T) in circulating leukocytes, and echocardiographic LV function data were compared between patients with HF New York Heart Association functional class II or III due to systolic dysfunction (n = 17), healthy controls (n = 17), and hypertensive patients without HF (n = 17). RESULTS In the control subjects, mean MYPT1-P/T ratio was 1.2 ± 0.2 (it was similar in the hypertensive patients without HF), whereas in patients with HF, it was significantly increased by >100-fold (P < .001). Both MYPT1-P/T and log MYPT1-P/T ratios were inversely correlated with ejection fraction (r = -0.54, P < .03 and r = -0.86, P < .001, respectively). Furthermore, in patients with HF with LV end-diastolic diameter <60 mm, MYPT1-P/T ratio was 35.8 ± 18.1, whereas it was significantly higher in patients with LV diameter ≥60 mm (P < .05). CONCLUSIONS Rho-Kinase activity is markedly increased in patients with stable chronic HF under optimal medical treatment, and it is associated with pathologic LV remodeling and systolic dysfunction. Mechanisms of Rho-kinase activation in patients with HF, its role in the progression of the disease, and the direct effect of Rho-kinase inhibition need further investigation.

Gender influence on the adaptation of atrial performance to training

Abstract Background: High-intensity training has been associated with atrial remodelling and arrhythmias in men. Our purpose was to analyse atrial performance in female endurance athletes, compared to male athletes and controls. Methods: This was a cross-sectional study. We included four groups: female athletes, females controls, male athletes and male controls. Left (LA) and right atrial (RA) volumes and function were assessed using 2D and speckle-tracking echocardiography to determine peak atrial strain-rate at atrial (SRa) and ventricular contraction (SRs), as surrogates of atrial contractile and reservoir function, respectively. ANOVA and Bonferroni’s statistical tests were used to compare variables among groups. Results: We included 82 subjects, 39 women (19 endurance athletes, 20 controls) and 43 men (22 endurance athletes, 21 controls). Mean age was similar between groups (36.6 ± 5.6 years). Athletes had larger bi-atrial volumes, compared to controls (women, LA 27.1 vs. 15.8 ml/m2, p < 0.001; RA 22.31 vs. 14.2 ml/m2, p = 0.009; men, LA: 25.0 vs. 18.5 ml/m2, p = 0.003; RA 30.8 vs. 21.9 ml/m2, p < 0.001) and lower strain-rate (women, LASRa −1.60 vs. −2.18 s−1, p < 0.001; RASRa −1.89 vs. −2.38 s−1, p = 0.009; men, LASRa −1.21 vs. −1.44 s−1, p = 1; RASRa −1.44 vs. −1.60 s−1, p = 1). However, RA indexed size was lower and bi-atrial deformation greater in female athletes, compared to male athletes. Conclusions: The atria of both male and female athletes shows specific remodelling, compared to sedentary subjects, with larger size and less deformation at rest, particularly for the RA. Despite a similar extent of remodelling, the pattern in women had greater bi-atrial myocardial deformation and smaller RA size.

Atrial Function Assessed by Speckle Tracking Echocardiography Is a Good Predictor of Postoperative Atrial Fibrillation in Elderly Patients

Advanced age is an independent predictor of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass surgery. We evaluated whether left atrial (LA) dysfunction assessed by strain contributes to identifying elderly patients prone to POAF.

Unidad de dolor torácico: primera experiencia en Chile

In large series, nearly 60% of admissions forsuspected acute coronary syndrome (ACS) had a non-coronary etiology of the pain. However,short term mortality of non recognized ACS patients, mistakenly discharged from the emergencyroom is at least twice greater than the expected if they would had been admitted. The concept ofa chest pain unit (CPU) is a methodological approach developed to address these issues.

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.