Heart Failure

A properly and flexibly functioning nervous system is necessary to maintain the most important cardiac function: the circulation of blood. The right side of the heart draws blood back from the tissues and propels the blood into the lungs to replenish oxygen and remove carbon dioxide. The oxygen-rich high-pressure left part of the heart receives blood via the lungs from the low-pressure oxygen-poor right part and then supplies the blood to all tissues and organs of the body. So, the heart circulates blood throughout the body. Heart failure is therefore considered as the inability of the heart to adequately maintain sufficient blood flow. Pooling of blood is usually the consequence and is coined "congestive" heart failure.

The consequences of heart failure will depend on which side of the heart is affected. An impaired function of the left ventricle (heart chamber) causes symptoms of fatigue and shortness of breath, especially during exercise. Malfunction of the right ventricle may cause swelling (edema) in the lower parts of the body (such as feet and legs). When the heart loses its ability to contract efficiently, the condition is called “systolic heart failure” or heart failure with reduced output i.e. ejection fraction (HFrEF). In contrast, when the heart fails to draw in enough blood (resulting from increased “stiffness”), the cardiac state is termed “diastolic failure”, or heart failure with preserved ejection fraction (HFpEF).

According to the American Heart Association, about 23 million people worldwide suffer from heart failure, a number that is almost equally divided between men and women (6). Heart failure in elderly women is frequently the result of long-term high blood pressure, resulting in heart failure with preserved output. In contrast, in men heart failure most often is the consequence of an impaired pump function, due to (corollaries of) coronary artery disease. Since more people are surviving coronary artery disease, more patients will develop heart failure.

Management of heart failure starts with treatment of the underlying cause. Much progress has been made in increasing therapeutic strategies. In accordance with the severity of heart failure, professional guidelines recommend lifestyle changes (for instance, eating healthy food, restricting salt and fluid intake, exercising more, and quitting smoking); medication (beta blockers, diuretics, renin-angiotensin-aldosterone system blockers, and vasodilators); and device implantation (implantable cardioverter defibrillator and cardiac resynchronization therapy). Ultimately, some patients may be considered for heart transplantation. Despite the best available care, patients with this medical condition still face a dim prognosis and poor quality of life. Furthermore, for some severely disabled patients due to their decreased heart function, current treatment options may become exhausted. In these patients suffering from heart failure and facing an increased risk of ventricular tachyarrhythmias (abnormal rapid heart rhythms), the autonomic nervous system plays a predominant role, since it controls cardiac functions. Overall, autonomic control optimizes and integrates such functions as heart rate (chronotropy), contractility (inotropy), relaxation (lusitropy) and conduction speed in specific parts of the heart (dromotropy). Consequently, like for patients with coronary artery disease, modulation of the autonomic nervous system has been explored as a possible additional therapy for heart failure patients who face a poor prognosis, in an attempt to improve their quality of life.

Evidence in both experimental and clinical observational studies with spinal cord stimulation (SCS), or stimulation of the vagal nerves, suggested those interventions might improve function of the heart. Unfortunately, the potential promise was not established in large randomized clinical trials that came to an end in 2015, DEFEAT-HF (SCS), and INOVATE-HF (vagus nerve stimulation). (1, 2). The discrepancy between experimental and most of the observational studies versus randomized control studies may be related to the site of stimulation, the unknown optimal parameter settings or the lack of clinical efficacy of neuromodulation of the autonomic nervous system on hard endpoints in patients with heart failure with reduced output (HFrEF). In contrast, an elegant systematic review in 2019 demonstrated a significant improvement in functional status and quality of life in 1,074 patients with HFrEF who were treated with device-based autonomic neurostimulation. (7). Furthermore, in August 2019, the U.S. FDA approved a neurostimulation device to treat heart failure with reduced ejection fraction in adults whose condition resists treatment with medication and who are not candidates for other device therapies for this condition. The implantable device stimulates the heart’s baroreceptor and was subject to a large clinical trial, BeAT-HF (Barostim Therapy for Heart Failure), initiated in 2016 (ClinicalTrials.gov Identifier: NCT02627196).

In summary, new evidence is coming available that neuromodulation may indeed be an effective additional therapy in patients suffering from heart failure with reduced ejection fraction.


1. http://www.clinicaltrials.gov/. (search key words: nerve and heart failure)

2. Mirnela Byku, Douglas L. Mann, Neuromodulation of the Failing Heart: Lost in Translation?, JACC: Basic to Translational Science, Volume 1, Issue 3, April 2016, Pages 95-106, ISSN 2452-302X, http://dx.doi.org/10.1016/j.jacbts.2016.03.004.

3. FDA. “FDA approves new device to improve symptoms in patients with advanced heart failure” FDA.gov, Aug. 16, 2019 https://www.fda.gov/news-events/press-announcements/fda-approves-new-device-improve-symptoms-patients-advanced-heart-failure.

4. Zipes DP, Neuzil P, Theres H, Caraway D, Mann DL, Mannheimer C, Van Buren P, Linde C, Linderoth B, Kueffer F, Sarazin SA, DeJongste MJ; Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Systolic Heart Failure: The DEFEAT-HF Study. DEFEAT-HF Trial Investigators. JACC Heart Fail. 2016 Feb;4(2):129-36. DOI: 10.1016/j.jchf.2015.10.006. Epub 2015 Dec 9.

5. Gold MR, Van Veldhuisen DJ, Hauptman PJ, Borggrefe M, Kubo SH, Lieberman RA, Milasinovic G, Berman BJ, Djordjevic S, Neelagaru S, Schwartz PJ, Starling RC, Mann DL. Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial. J Am Coll Cardiol. 2016 Mar 29. pii: S0735-1097(16)32404-4. DOI: 10.1016/j.jacc.2016.03.525. [Epub ahead of print]

6. Roger VL. Epidemiology of heart failure. Circ Res. 2013 Aug 30;113(6):646-59.
doi: 10.1161/CIRCRESAHA.113.300268. Review. PubMed PMID: 23989710; PubMed Central PMCID: PMC3806290.

7. Bendary A, Bendary M, Salem M. Autonomic regulation device therapy in heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials. Heart Failure Reviews (2019) 24:245–254

Reviewed May 27, 2016
Mike JL DeJongste, MD, PhD
Executive Officer, International Neuromodulation Society, 1994 - 2003

Department of Cardiology, University Hospital Groningen, Groningen, The Netherlands


Last Updated on Sunday, November 21, 2021 08:17 PM