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International Journal of Physical Medicine & Rehabilitation

International Journal of Physical Medicine & Rehabilitation
Open Access

ISSN: 2329-9096

+44 1300 500008

Commentary - (2022)Volume 10, Issue 3

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Prognosis of Heart Failure and Sympathetic Nerve Activity

Shinya Minatoguchi1,2*
 
*Correspondence: Shinya Minatoguchi, Department of Circulatory and Respiratory Advanced Medicine, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu City, Gifu 501-1194, Japan, Email:

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Abstract

The prognosis of heart failure is poor and plasma noradrenaline level is a good predictor of the survival rate of heart failure patients. Sympathetic nerve activity is augmented in patients with heart failure as evidenced by a higher noradrenaline release rate from the sympathetic nerve endings. Drugs for heart failure such as β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid antagonists, ivabradine, Angiotensin Receptor-Neprilysin Inhibitor (ARNI), and Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors have clinical evidences for improving prognosis of heart failure in large randomized-controlled clinical trials. Interestingly, the same characteristics in common of these drugs is to reduce sympathetic nerve activity. In addition, cardiac rehabilitation which causes a better prognosis of heart failure reduces the sympathetic nerve activity. In conclusion, to optimize excessively augmented sympathetic nerve activity may be related to an improvement of prognosis of heart failure.

Keywords

Heart failure; Sympathetic nerve activity; Prognosis; Anti-heart failure drugs; Cardiac rehabilitation

About the Study

Heart failure is the end-stage phenotype of all kinds of cardiac diseases. The 5-year death rate of heart failure with a New York Heart Association functional classification (NYHA) IV (SCONSENSUS placebo) is comparable to lung cancer (Stage IIIA), and heart failure with NYHA II-III (Studies of Left Ventricular Dysfunction (SOLVD)-T placebo) or NYHA I-II (SOLVD-P placebo) to cancers such as stomach (Stage III), breast (Stage IIIA), and colorectal cancer (Dukes C) [1-3]. Since the prognosis of heart failure is very poor, to know what is the main factor that deteriorates prognosis of heart failure is important.

Plasma noradrenaline level is a prognostic factor of heart failure patients

Plasma noradrenaline levels are inversely correlated with cardiac index or Left Ventricular Ejection Fraction (LVEF) [4]. Plasma noradrenaline levels increase according to the severity of heart failure based on the NYHA classification [5]. These suggest that deterioration of LV function causes higher plasma noradrenaline levels in patients with heart failure. Plasma noradrenaline level has been reported to be a powerful predictor of the survival rate of heart failure patients [6,7]. Higher plasma noradrenaline level is a predictor of poor prognosis even in HFpEF patients [8]. Plasma noradrenaline level is determined by the balance between noradrenaline release rate from the sympathetic nerve endings and noradrenaline clearance rate from the blood [9]. Thus, to assess real sympathetic nerve activity, noradrenaline release rate (spillover rate) from the sympathetic nerve endings should be measured. In the rabbit model of heart failure, noradrenaline release rate was significantly greater than the control rabbits [9]. Furthermore, noradrenaline release rate was significantly higher in patients with heart failure than in the control, and the increase in noradrenaline release was mainly due to the heart and kidney [10].

Pharmacological therapies for heart failure patients

There are clinical evidences that anti-heart failure drugs show a better prognosis;

Beta blockers (CIBS-II, MERIT-HF, COPERNICUS) [11-13], ACE inhibitors (CONSENSUS, SOLVED) [14,15], ARBs (Val- HeFT) [16], MRAs (RALES, EMPHASIS-HF) [17,18], Ivabradine (SHIFT) [19], ARNI (PARADIGM-HF) [20], SGLT2 inhibitors (DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved) [21-23].

Effects of anti-heart failure drugs on sympathetic nerve activity

Beta-blockers block the sympathetic nerve activity at the postsynaptic beta-receptors. Captopril, an ACE inhibitor, and saralasin, an ARB decrease the noradrenaline release rate [24]. In an animal study of rabbits with heart failure, captopril decreased the noradrenaline release rate from the sympathetic nerve endings when corrected by hypotensive reflex [9]. In rats with heart failure induced by angiotensin II-infusion and saltloading, chronic treatment with telmisartan, an ARB, significantly decreased the urinary noradrenaline level compared with the control [25]. In an animal study with rats, eplerenone, an MRA, decreased renal sympathetic nerve activity, which was recorded by stainless steel bipolar electrodes placed beneath the renal nerve [26]. In heart failure rats induced by coronary artery ligation, administration of ivabradine significantly decreased the plasma noradrenaline levels than in an untreated group [27]. ARNI produces BNP by blocking the enzyme neprilysin by sacubitril and blocks Ang II-receptors by valsartan. ARB decreases noradrenaline release rate [24]. It was reported that BNP decreased noradrenaline release in response to sympathetic nerve stimulation in an isolated atria preparation [28], and that infusion of BNP decreased noradrenaline release rate in patients with heart failure [29], suggesting that ARNI decreases sympathetic nerve activity. In Schlager mice (BPH/2J strain), oral administration of dapagliflozin reduced the sympathetic innervation in the kidney assessed by tyrosine hydroxylase staining, and reduced the noradrenaline content in the kidney as comparted with the control [30]. In HFpEF pigs induced by infusion of a combination of deoxycorticosterone and Ang II, dapagliflozin treatment decreased the expression of tyrosine hydroxylase and tissue content of noradrenaline in the aorta [31]. In ApoE-/-mice fed a western diet for 12 weeks, treatment with 10 mg/kg/day of oral empagliflozin for 12 weeks reduced the plasma noradrenaline levels significantly as compared with mice without treatment with empagliflozin [32].

All these reports mentioned above suggest that beta-blockers, ACE inhibitors, ARBs, MRAs, Ivabradine, ARNI and SGLT2 inhibitors have ability to reduce excessively augmented sympathetic nerve activity.

Cardiac rehabilitation

It has been reported that cardiac rehabilitation improves prognosis of heart failure patients [33]. It has been reported that bicycle exercise training for one month reduces plasma noradrenaline levels and total spillover rate of noradrenaline in healthy subjects [34] and that exercise training reduces the muscle sympathetic nerve activity in patients with heart failure [35]. The reduction of sympathetic nerve activity may be related to an improvement of prognosis of patients with heart failure.

Clinical perspective

Heart failure patients with a higher plasma noradrenaline level show a poor survival rate [6,7], suggesting that excessively augmented sympathetic nerve activity is involved in the poor survival rate of heart failure patients. Treatment to optimize excessively augmented sympathetic nerve activity may be an essential treatment for heart failure to improve the poor survival rate.

Conflict of Interest

There is no conflict of interest to be declared.

References

Author Info

Shinya Minatoguchi1,2*
 
1Heart Failure Center, Gifu Municipal Hospital, Kashimacho 7-1, Gifu City, Gifu 500-8513, Japan
2Department of Circulatory and Respiratory Advanced Medicine, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu City, Gifu 501-1194, Japan
 

Citation: Minatoguchi S (2022) Prognosis of Heart Failure and Sympathetic Nerve Activity. Int J Phys Med Rehabil. 10:628.

Received: 23-Feb-2022, Manuscript No. JPMR-22-15989; Editor assigned: 25-Feb-2022, Pre QC No. JPMR -22-15989 (PQ); Reviewed: 11-Mar-2022, QC No. JPMR B-22-15989; Revised: 16-Mar-2022, Manuscript No. JPMR -22-15989 (R); Published: 23-Mar-2022 , DOI: 10.35248/2329-9096.22.10.628

Copyright: © 2022 Minatoguchi S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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