1,721,093 research outputs found

    Eplerenone in chronic heart failure with depressed systolic function

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    Eplerenone is a selective mineralocorticoid receptor antagonist that has been recently included in the treatment of patients with chronic heart failure (CHF) and reduced systolic function. This brief review aims to summarize current evidence on the role of eplerenone in the therapy of patients with CHF. In the EPHESUS trial, 6632 post-myocardial infarction patients with ejection fraction (EF) < 40% and clinical HF signs were randomized to eplerenone or placebo added to standard therapy 3 to 14 days after the event. After a 16 month follow-up period, eplerenone given early (< 7 days) reduced the primary endpoints of all-cause mortality by 15% and cardiovascular death or cardiovascular hospitalization by 13%. In the subsequent EMPHASIS-HF trial, the efficacy and tolerability of eplerenone were tested in patients with mild CHF (NYHA functional class II) and EF< 30% or between 30 and 35% with QRS duration > 130 ms. After a median follow-up of 21 months eplerenone significantly reduced (by 37%) the primary composite outcome of risk of death from CV causes and first hospitalization for HF. Based on the above findings, the addition of eplerenone to standard therapy, at doses to be titrated from 25 to 50 mg per day, is currently recommended in CHF patients with functional classes II to IV closely resembling those enrolled in these large clinical trials, with adequate monitoring for side effects (mainly hyperkalemia and renal failure). Whether the same beneficial effects of eplerenone extend to CHF patients with mild symptoms and no additional risk factors are unknown

    Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight

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    Di Rienzo M, Castiglioni P, Iellamo F, Volterrani M, Pagani M, Mancia G, Karemaker JM, Parati G. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight. J Appl Physiol 105: 1569-1575, 2008. First published August 28, 2008; doi:10.1152/japplphysiol.90625.2008.-This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Columbia Space Shuttle mission. Continuous blood pressure (BP), ECG, and respiratory frequency were collected in four astronauts on ground (baseline) and during flight at days 0-1, 6-7, and 12-13, both at rest and during moderate exercise (75 W) on a cycle ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI); low-frequency (LF) power and high-frequency (HF) power of systolic BP (SBP), diastolic BP (DBP), and R-R interval (RRI); the RRI LF/HF ratio; and the RRI root mean square of successive differences (RMSSD) index were also estimated. We found that, at rest, BRS increased in early flight phase, compared with baseline (means +/- SE: 18.3 +/- 3.4 vs. 10.4 +/- 1.2 ms/mmHg; P < 0.05), and it tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between preflight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (P < 0.05) compared with baseline, whereas LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. These findings demonstrate that heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart

    Uric acid lowering therapy in cardiovascular diseases

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    Recent evidence would indicate that high serum uric acid (SUA) levels can be a significant and independent risk factor for hypertension and cardiovascular diseases, such as ischemic heart disease and heart failure. In the last few years an independent risk relationship between hyperuricemia, cardiovascular disease and mortality has also been reported. Hyperuricemia has been shown as an independent risk factor for acute myocardial infarction and an independent and conjoint association of either gout and SUA with total and cardiovascular mortality has been reported, with mortality impact in gout patients increasing with rising SUA concentrations, even for SUA levels in the normal to high range. These findings prompted a growing research interest on the possible benefits of uric acid lowering drugs in cardiovascular diseases. Indeed, clinical studies have reported on the beneficial effects of uric acid lowering drugs, in particular of xanthine oxidase inhibitors, in hypertension, ischemic heart disease and heart failure. Two main mechanisms have been claimed to explain the dangerous effects of hyperuricemia and, as a consequence, the benefits of uric acid lowering therapy: endothelial dysfunction and systemic inflammation. This brief review aims to summarize current evidence from human studies on the role of acid uric lowering therapy in cardiovascular diseases for practical and clinical purposes. The possible mechanisms underlying the benefits of acid uric lowering therapy are also addressed

    Therapeutic options of Angiotensin Receptor Neprilysin inhibitors (ARNis) in chronic heart failure with reduced ejection fraction: Beyond RAAS and sympathetic nervous system inhibition

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    In heart failure, in addition to the renin–angiotensin–aldosterone system and sympathetic nervous system, the natriuretic peptide (NP) system plays a fundamental role among compensating mechanisms. The NPs undergo rapid enzymatic degradation that limits their vasorelaxant, natriuretic, and diuretic actions. Degradation of NPs is partially due to the action of neprilysin, which is a membrane-bound endopeptidase found in many tissues. This article summarizes recent findings on a new natriuretic peptide-enhancing drug and their implication for future pharmacological treatment of patients suffering from heart failure with reduced ejection fraction

    Nonlinear heart rate control in treadmill/cycle-ergometer exercises under the instability constraint

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    The heart rate regulation problem is addressed for the well-known second order nonlinear model of the human heart rate response during treadmill/cycle-ergometer exercises. The mainly restrictive stability &amp; global attractivity constraint in the literature, being constituted by an inequality involving four constant parameters of such a nonlinear model, is definitely removed. Nonlinear analytical arguments and design steps are innovatively presented to achieve heart rate regulation when model parameters satisfy the so-called 'instability constraint', with just stability &amp; local attractivity properties being involved. Experimental results are included to illustrate all the theoretical derivations. (C) 2021 Elsevier Ltd. All rights reserved
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