Sympathetic neural responses in heart failure during exercise and after exercise training

2021 ◽  
Vol 135 (4) ◽  
pp. 651-669
Author(s):  
Catherine F. Notarius ◽  
John S. Floras

Abstract The sympathetic nervous system coordinates the cardiovascular response to exercise. This regulation is impaired in both experimental and human heart failure with reduced ejection fraction (HFrEF), resulting in a state of sympathoexcitation which limits exercise capacity and contributes to adverse outcome. Exercise training can moderate sympathetic excess at rest. Recording sympathetic nerve firing during exercise is more challenging. Hence, data acquired during exercise are scant and results vary according to exercise modality. In this review we will: (1) describe sympathetic activity during various exercise modes in both experimental and human HFrEF and consider factors which influence these responses; and (2) summarise the effect of exercise training on sympathetic outflow both at rest and during exercise in both animal models and human HFrEF. We will particularly highlight studies in humans which report direct measurements of efferent sympathetic nerve traffic using intraneural recordings. Future research is required to clarify the neural afferent mechanisms which contribute to efferent sympathetic activation during exercise in HFrEF, how this may be altered by exercise training, and the impact of such attenuation on cardiac and renal function.

2015 ◽  
Vol 40 (11) ◽  
pp. 1107-1115 ◽  
Author(s):  
Catherine F. Notarius ◽  
Philip J. Millar ◽  
John S. Floras

The sympathetic nervous system is critical for coordinating the cardiovascular response to various types of physical exercise. In a number of disease states, including human heart failure with reduced ejection fraction (HFrEF), this regulation can be disturbed and adversely affect outcome. The purpose of this review is to describe sympathetic activity at rest and during exercise in both healthy humans and those with HFrEF and outline factors, which influence these responses. We focus predominately on studies that report direct measurements of efferent sympathetic nerve traffic to skeletal muscle (muscle sympathetic nerve activity; MSNA) using intraneural microneurographic recordings. Differences in MSNA discharge between subjects with and without HFrEF both at rest and during exercise and the influence of exercise training on the sympathetic response to exercise will be discussed. In contrast to healthy controls, MSNA increases during mild to moderate dynamic exercise in the presence of HFrEF. This increase may contribute to the exercise intolerance characteristic of HFrEF by limiting muscle blood flow and may be attenuated by exercise training. Future investigations are needed to clarify the neural afferent mechanisms that contribute to efferent sympathetic activation at rest and during exercise in HFrEF.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Andreas B. Gevaert ◽  
Katrien Lemmens ◽  
Christiaan J. Vrints ◽  
Emeline M. Van Craenenbroeck

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF.


2021 ◽  
Author(s):  
Mohammad Abumayyaleh ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Christina Pilsinger ◽  
Katherine Sattler ◽  
...  

The treatment with sacubitril/valsartan in patients suffering from chronic heart failure with reduced ejection fraction increases left ventricular ejection fraction and decreases the risk of sudden cardiac death. We conducted a retrospective analysis regarding the impact of age differences on the treatment outcome of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction. Patients were defined as adults if ≤65 years (n = 51) and older if >65 years of age (n = 76). The incidence of ventricular arrhythmias at 1-year follow-up was comparable in both groups (30.8 vs 26.5%; p = 0.71). The mortality rate in adult patients is significantly lower as compared with older patients (2 vs 14.5%; log-rank = 0.04). Older patients may suffer remarkably more side effects than adult patients (21.1 vs 11.8%; p = 0.03).


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
A Cho ◽  
S Prausmueller ◽  
G Spinka ◽  
J Novak ◽  
...  

Abstract Background Elevated inflammatory markers and malnutrition are characteristic for heart failure with reduced ejection fraction (HFrEF) correlating with disease severity and prognosis. Nutritional decline is closely linked to inflammation. Evidence emerges that heart failure can be triggered by inflammation directly, meaning that progression of HF is a function of individual inflammatory host response. We aimed to investigate and compare the impact of well-established inflammation based scores and inflammation-related nutritional scores on survival in HFrEF. Methods Stable HFrEF-patients undergoing routine ambulatory care between 2011 and 2017 have been identified from a prospective registry. Comorbidities and laboratory data at baseline were assessed. All-cause mortality was defined the primary endpoint. The modified Glasgow Prognostic Score (mGPS: 0/1/2 based on CRP and albumin), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) as well as the Nutritional Risk Index (NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight (kg)) and the Prognostic Nutritional Index (PNI = albumin (g l–1) × total lymphocyte count × 109 l–1) were calculated. The association of the scores with HF severity and impact on overall survival were determined. Results Data of 443 patients receiving well titrated guideline directed HF therapy have been analyzed. Median age was 64 years (IQR 53–72), 73% were male. Median body mass index (BMI) was 26.6kg/m2 (IQR 23.8–30.2), median NT-proBNP was 2053pg/ml (IQR 842–4345) with most patients presenting in NYHA class II (178, 40%) and III (173, 39%). The mGPS was 0 for 352 (80%), 1 for 76 (17%) and 2 for 14 (3%) patients, respectively. All scores correlated with HF severity reflected by NT-proBNP [p<0.001 for mGPS, r=−0.48; p<0.001 for PNI] and NYHA class [p<0.001 for mGPS and PNI]. All scores were associated with all-cause mortality in univariate analysis. After adjustment for age, gender and kidney function only mGPS, PLR, NRI and PNI remained significantly associated with outcome. Out of these the ROC were highest for PNI and mGPS [0.674 and 0.652 respectively] and solely these scores remained significantly associated with mortality after including NT-proBNP in the multivariate model [adj.HR 1.87 (95% CI: 1.20–2.91), p=0.006 for mGPS; 0.62 (95% CI: 0.40–0.96), p=0.032 for PNI]. Kaplan Meier analysis confirmed the discriminatory power of mGPS and PNI (Figure 1). Conclusions Enhanced inflammation and malnutrition are more common in advanced heart failure. Among established inflammation and nutritional scores merely mGPS and PNI are associated with survival in HFrEF patients independently of NT-proBNP. This relationship emphasizes the significance of the individual proinflammatory response on prognosis.This easily available score may help clinicians to identify HFrEF patients with worse prognosis with urgent need for intensified therapy and/or alternate treatment options.


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