Do high doses of AT1-receptor blockers attenuate central sympathetic outflow in humans with chronic heart failure?

2013 ◽  
Vol 124 (9) ◽  
pp. 589-595 ◽  
Author(s):  
Marcel Ruzicka ◽  
John S. Floras ◽  
Andrew J. G. McReynolds ◽  
Elizabeth Coletta ◽  
Haissam Haddad ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Muscle Sympathetic Nerve Activity ◽  
Plasma Catecholamines ◽  
Heart Association ◽  
At1 Receptor ◽  
Sympathetic Outflow ◽  
Receptor Blockers ◽  
Central Sympathetic Outflow ◽  
At1 Receptor Blockers

In patients with CHF (chronic heart failure) sympathetic activity increases as cardiac performance decreases and filling pressures increase. We hypothesized that in patients with mild-to-moderate CHF, higher than conventional doses of an AT1-receptor [AngII (angiotensin II) type 1 receptor] antagonist would achieve greater central AT1-receptor blockade, resulting in diminished MSNA (muscle sympathetic nerve activity) and augmented MSNA variability, two indices of central effects on sympathetic outflow. In total, 13 patients with ischaemic cardiomyopathy [NYHA (New York Heart Association) class II–III] were weaned off all pharmacological RAS (renin–angiotensin system) modifiers, and then randomized to receive a low (50 mg/day) or high (200 mg/day) dose of losartan. Central haemodynamics, MSNA and its variability, plasma catecholamines, AngI (angiotensin I) and AngII and aldosterone were assessed both before and 3 months after randomization. Neither dose altered BP (blood pressure), PCWP (pulmonary capillary wedge pressure) or CI (cardiac index) significantly. Compared with 50 mg daily, losartan 200 mg/day decreased MSNA significantly (P<0.05), by approximately 15 bursts/min, and increased MSNA variability within the 0.27–0.33 Hz high-frequency range by 0.11 units2/Hz (P=0.06). PNE [plasma noradrenaline (norepinephrine)] fell in parallel with changes in MSNA (r=0.62; P<0.05). These findings support the hypothesis that higher than conventional doses of lipophilic ARBs (AT1-receptor blockers) can modulate the intensity and variability of central sympathetic outflow in patients with CHF. The efficacy and safety of this conceptual change in the therapeutic approach to heart failure merits prospective testing in clinical trials.

scholarly journals Association between ventilatory efficiency, oxygen uptake, and Glittre-ADL test results in patients with chronic heart failure: a preliminary study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hebert Olímpio Júnior ◽  
Agnaldo José Lopes ◽  
Fernando Silva Guimarães ◽  
Sergio Luiz Soares Marcos da Cunha Chermont ◽  
Sara Lúcia Silveira de Menezes
Keyword(s):  
Heart Failure ◽  
New York ◽  
Chronic Heart Failure ◽  
Functional Capacity ◽  
Treatment Plan ◽  
Minute Ventilation ◽  
Heart Association ◽  
Gas Analysis ◽  
Ventilatory Efficiency ◽  
Scale Scores

Abstract Objective The Glittre-ADL test (GA-T) is a functional capacity test that stands out for encompassing multiple tasks similar to activities of daily living. As ventilatory efficiency is one of the variables valued in the prognosis of chronic heart failure (CHF), this study aimed to evaluate associations between functional capacity and ventilatory variables in patients with CHF during the GA-T. Results Eight patients with CHF and New York Heart Association (NYHA) functional classification II–III underwent the GA-T coupled with metabolic gas analysis to obtain data by means of telemetry. The median total GA-T time was 00:04:39 (00:03:29–00:05:53). Borg dyspnoea scale scores before and after the GA-T were 2 (0–9) and 3 (1–10), respectively (P = 0.011). The relationship between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) was correlated with the total GA-T time (rs = 0.714, P = 0.047) and Borg dyspnoea score (rs = 0.761, P = 0.028). The other ventilatory variables showed no significant correlations. Our results suggest that the total GA-T time can be applied to estimate the ventilatory efficiency of patients with CHF. Future studies may use the GA-T in conjunction with other functional capacity tests to guide the treatment plan and evaluate the prognosis.

scholarly journals Remote monitoring of chronic heart failure patients: invasive versus non-invasive tools for optimising patient management

2019 ◽  
Vol 28 (1) ◽  
pp. 3-13 ◽  
Author(s):  
J. F. Veenis ◽  
J. J. Brugts
Keyword(s):  
Heart Failure ◽  
New York ◽  
Chronic Heart Failure ◽  
Remote Monitoring ◽  
Heart Association ◽  
The United States ◽  
Pharmacological Therapy ◽  
Functional Class ◽  
Class Iii ◽  
Additional Tool

AbstractExacerbations of chronic heart failure (HF) with the necessity for hospitalisation impact hospital resources significantly. Despite all of the achievements in medical management and non-pharmacological therapy that improve the outcome in HF, new strategies are needed to prevent HF-related hospitalisations by keeping stable HF patients out of the hospital and focusing resources on unstable HF patients. Remote monitoring of these patients could provide the physicians with an additional tool to intervene adequately and promptly. Results of telemonitoring to date are inconsistent, especially those of telemonitoring with traditional non-haemodynamic parameters. Recently, the CardioMEMS device (Abbott Inc., Atlanta, GA, USA), an implantable haemodynamic remote monitoring sensor, has shown promising results in preventing HF-related hospitalisations in chronic HF patients hospitalised in the previous year and in New York Heart Association functional class III in the United States. This review provides an overview of the available evidence on remote monitoring in chronic HF patients and future perspectives for the efficacy and cost-effectiveness of these strategies.

scholarly journals (Pro)renin receptor: another member of the system controlled by angiotensin II?

2011 ◽  
Vol 13 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Luciana G Pereira ◽  
Carine P Arnoni ◽  
Edgar Maquigussa ◽  
Priscila C Cristovam ◽  
Juliana Dreyfuss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Mesangial Cells ◽  
At1 Receptor ◽  
Receptor Internalization ◽  
Prorenin Receptor ◽  
Receptor Blockers ◽  
And Function ◽  
At1 Receptor Blockers

The prorenin receptor [(P)RR] is upregulated in the diabetic kidney and has been implicated in the high glucose (HG)-induced overproduction of profibrotic molecules by mesangial cells (MCs), which is mediated by ERK1/2 phosphorylation. The regulation of (P)RR gene transcription and the mechanisms by which HG increases (P)RR gene expression are not fully understood. Because intracellular levels of angiotensin II (AngII) are increased in MCs stimulated with HG, we used this in vitro system to evaluate the possible role of AngII in (P)RR gene expression and function by comparing the effects of AT1 receptor blockers (losartan or candesartan) and (P)RR mRNA silencing (siRNA) in human MCs (HMCs) stimulated with HG. HG induced an increase in (P)RR and fibronectin expression and in ERK1/2 phosphorylation. These effects were completely reversed by (P)RR siRNA and losartan but not by candesartan (an angiotensin receptor blocker that, in contrast to losartan, blocks AT1 receptor internalization). These results suggest that (P)RR gene activity may be controlled by intracellular AngII and that HG-induced ERK1/2 phosphorylation and fibronectin overproduction are primarily induced by (P)RR activation. This relationship between AngII and (P)RR may constitute an additional pathway of MC dysfunction in response to HG stimulation.

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