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EURO PEAN
SO CIETY O F
Original Scientific Paper CARDIOLOGY ®

European Journal of Preventive

Cardiology

Efficacy and safety of functional electrical 0(00) 1–6

! The European Society of
Cardiology 2014
stimulation of lower limb muscles in Reprints and permissions:
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elderly patients with chronic heart failure: DOI: 10.1177/2047487314540546
ejpc.sagepub.com
A pilot study

John Parissis1, Apostolos Karavidas2, Dimitrios Farmakis1,

Nikolaos Papoutsidakis2, Vassiliki Matzaraki2, Sofia Arapi2,
Nikolaos Potamitis2, Maria Nikolaou1, Ioannis Paraskevaidis1,
Ignatios Ikonomidis1, Vlassios Pyrgakis2,
Dimitrios Kremastinos1, John Lekakis1 and
Gerasimos Filippatos1

Abstract
Background: Exercise training is an established modality in chronic heart failure. Functional electrical stimulation (FES)
is an effective alternative mode of training in patients unwilling or unable to exercise; however, it has not been
investigated in elderly patients. We sought to investigate the effects of FES on functional status, quality of life, emotional
status and endothelial function in chronic heart failure patients aged 70 years or higher.
Methods: Thirty patients with stable systolic chronic heart failure (mean age 75  3 years, New York Heart Association
(NYHA) class II/III, 37%/63%) randomly underwent a six-week FES training programme or placebo. Questionnaires
addressing quality of life (Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall) and emotional
stress (Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)), as well as endothelial function (flow-
mediated dilatation) were assessed at baseline and upon protocol completion.
Results: A significant improvement in NYHA class (p ¼ 0.005), KCCQ-functional (F ¼ 68.6, p for interaction < 0.001),
KCCQ-overall (F ¼ 66.9, p < 0.001), BDI (F ¼ 66.3, p < 0.001) and Zung SDS (F ¼ 95.1, p < 0.001) was observed in the
FES group compared to placebo. Patients in the FES group also had a significant increase in flow-mediated dilatation
compared with placebo (F ¼ 59.1, p < 0.01). FES-induced per cent change in flow-mediated dilatation was significantly
correlated with respective per cent change in KCCQ functional (r ¼ 0.386, p ¼ 0.039).
Conclusion: In this pilot study, FES effectively improved functional status, quality of life, motional stress and endothelial
function in elderly chronic heart failure patients and warrants further investigation in this particular group of patients.

Keywords
Heart failure, exercise, rehabilitation, functional electrical stimulation, elderly
Received 19 March 2014; accepted 2 June 2014

Introduction
The most frequent complaint of patients suffering from 1
Heart Failure Unit, Department of Cardiology, Attikon University
chronic heart failure (CHF) is exercise intolerance. This Hospital, Athens, Greece
2
symptom is so ubiquitous and well correlated with the Department of Cardiology, G Gennimatas Hospital, Athens, Greece
severity of CHF that it alone is used for the most popu-
Corresponding author:
lar CHF severity scale, New York Heart Association Dimitrios Farmakis, Heart Failure Unit, Department of Cardiology,
(NYHA) class. Although there are very good pharma- Attikon University Hospital, 1 Rimini St, Athens, Greece.
ceutical choices for symptom alleviation, such as Email: dimitrios_farmakis@yahoo.com

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2 European Journal of Preventive Cardiology 0(00)

diuretics, CHF patients often adopt a more sedentary versa. The patients were trained for 30 min a day, five
lifestyle, both to avoid feelings of dyspnoea and fatigue days per week for a total of six weeks. The placebo
and to preserve what they consider to be a ‘diseased group was exposed to the same regimen as the FES
heart’. The European Society of Cardiology guidelines group, using a lower intensity of stimulation (5 Hz)
address this common misperception by recommending that did not lead to visible or palpable contractions,
aerobic exercise training to all stable CHF patients.1 In as judged objectively or subjectively.
practice, however, some patients are unable – due to In addition, all subjects were asked to complete
increased exercise intolerance – or unwilling to partici- questionnaires to assess quality of life (Kansas City
pate in such programmes. Cardiomyopathy Questionnaire (KCCQ), functional
Functional electrical stimulation (FES), a modality and overall) and screen emotional stress (Zung self-
that causes muscular contraction through electrical rating depression scale (SDS), Beck Depression
stimulation, has been shown to improve functional Inventory (BDI)), both at the baseline evaluation and
status, exercise capacity, endothelial function, quality after completion of the training programme.7–9
of life and emotional stress as well as patients’ adher- Endothelial function was assessed by a high-resolution
ence to rehabilitation programmes, thus constituting an ultrasound system (Philips HDI 5000 Sonos CT) and an
alternative approach in patients who are unable or 8 MHz linear-array transducer, as described in detail
unwilling to exercise.2–5 The corresponding studies on elsewhere. Endothelium-dependent brachial artery
FES in CHF have generally enrolled patients up to flow-mediated dilatation (FMD) was determined as
their sixth decade of life, with the oldest trial popula- described previously.10,11
tion being on average 63  10 years old.2 However, eld-
erly patients are probably in greater need of an
Statistical analysis
alternative training programme, as they have a greater
difficulty in adhering to a physical exercise regime com- Statistical analysis was performed using the SPSS 18.0
pared with younger patients due to reduced physical statistical software package (SPSS Inc., Chicago, IL,
activity, significant comorbidities and increased feelings USA). Categorical variables are expressed as percent-
of anxiety and depression.6 ages of the corresponding population and continuous
Bearing in mind the above, we sought to examine variables are expressed as mean values. Continuous
whether FES is safe and efficacious in improving func- variables were tested for normal distribution by the
tional status, quality of life, emotional status and endo- Kolmogorov–Smirnov test. The t-test for independent
thelial function in CHF patients aged 70 years and samples was used to compare means of continuous
above. variables while the Mann–Whitney U test was appro-
priate for non-normally distributed variables. General
linear model for repeated measurements was used to
Methods assess the effect of FES treatment on different variables
The study population included 30 consecutive patients in the two study groups. A p value <0.05 was con-
with stable systolic CHF (NYHA class II or III, left sidered statistically significant.
ventricular ejection fraction <40%), who underwent
randomly (1:1) a six-week FES training programme
or placebo treatment. The study protocol was approved
Results
by the institutional Ethics Committee and all patients Patients’ characteristics at baseline are shown in Table 1.
gave written informed consent. No significant differences were encountered between the
A detailed description of the FES protocol can be FES group and the placebo group. No adverse events
found elsewhere.3–5 In brief, eight adhesive electrodes related to exercise training were reported by either the
(size, 50 mm  90 mm) were positioned on the skin over patient or the physicians during the study period in
the upper lateral and lower medial aspects of the quad- either of the two groups. The effects of treatment are
riceps muscle of both legs and over the upper and lower summarized in Table 2. Mean per cent changes in
portions of the gastrocnemius muscles of both legs. In study parameters observed during the study period are
the FES group, the stimulator was configured to deliver shown in Figure 1. Patients in the FES group had a
a direct electrical current at 25 Hz for 5 s followed by a significant improvement in NYHA class (p ¼ 0.005),
5-s rest. The intensity of the stimulation was adjusted to KCCQ-functional score (F ¼ 68.6, p for the interaction
achieve a visible muscle contraction that was not suffi- <0.001), KCCQ-summary score (F ¼ 66.9, p < 0.001),
ciently strong to cause discomfort or a significant BDI (F ¼ 66.3, p < 0.001) and Zung SDS (F ¼ 95.1,
movement at either the knee or the ankle joints. p < 0.001) compared with placebo. Moreover, FMD
When the muscles of the right leg were contracted, was also significantly improved in the FES group com-
the muscles of the left leg were relaxing and vice pared with placebo (F ¼ 59.1, p < 0.01). FES-induced

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Parissis et al. 3

Table 1. Baseline characteristics in study groups; there were no statistically significant differences between functional electrical
stimulation (FES) group and placebo group.

All subjects FES group Placebo group

Number of patients 30 15 15
Demographics
Female gender 10 (33%) 4 (27%) 6 (40%)
Age, years 75.2  3.5 75.2  3.68 75.2  3.32
LVEF, % 27.6  2.8 27.3  3.2 28  2.5
NYHA class, II/III 11 (37%)/19 (63%) 5 (33%)/10 (67%) 6 (40%)/9 (60%)
Medication
ACE inhibitor or ARB 26 (87%) 12 (80%) 14 (93%)
b-blockers 28 (93%) 15 (100%) 13 (87%)
Diuretics 28 (93%) 13 (87%) 15 (100%)
Risk factors
Diabetes mellitus 9 (30%) 5 (33%) 4 (27%)
Hypertension 14 (47%) 5 (33%) 9 (60%)
Hyperlipidaemia 14 (47%) 8 (53%) 6 (40%)
Ever smoked 19 (63%) 11 (74%) 8 (54%)
Body mass index >25 kg/m2 12 (40%) 5 (33%) 7 (47%)
Number of risk factors 2.9  0.9 2.9  0.9 2.9  1.1
LVEF: left ventricular ejection fraction; ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker.

Table 2. Effects of treatment (functional electrical stimulation (FES) versus placebo) on functional status, quality of life, emotional
status and endothelial function.

FES group Placebo group

Baseline Post treatment Baseline Post treatment F p

NYHA, II/III 33%/67% 73%/27% 40%/60% 20%/80% 0.005a

KCCQ-f 50,6  26,6 71.7  20.4 60.7  23.0 57.9  24.7 68.6 <0.001b
KCCQ-s 42.9  26.1 67.3  20.5 56.1  23.6 53.2  25.9 66.9 <0.001b
BDI 12.3  3.4 8.5  2.1 11.6  3.2 12.0  2.7 66.3 <0.001b
Zung SDS 38  6 30  6 37  6 39  6 95.1 <0.001b
FMD 0.15  0.08 0.33  0.15 0.17  0.07 0.15  0.07 59.1 <0.01b
NYHA: New York Heart Association class; KCCQ-f: Kansas City Cardiomyopathy Questionnaire-functional score; KCCQ-s: Kansas City
Cardiomyopathy Questionnaire-summary score; BDI: Beck Depression Inventory; Zung SDS: Zung self-rating depression scale; FMD: flow-mediated
dilatation; a2 test FES versus placebo post treatment.; bp value for the interaction.

change in FMD was significantly correlated with The benefits of exercise in the elderly are well docu-
respective change in KCCQ-functional score mented, especially regarding cardiovascular health and
(r ¼ 0.386, p ¼ 0.039). exercise tolerance in CHF patients.12–14 The first large-
scale examination of exercise training potential for
CHF patients was made in the HF-ACTION trial,15 a
Discussion randomized trial that enrolled 2331 stable patients with
In the present pilot study, FES was a safe and effica- systolic CHF and mild to moderately severe symptoms.
cious alternative to physical exercise training in older Because this trial employed an intensive regime of aer-
CHF patients. FES was followed by a significant obic exercise (36 supervised sessions within three
improvement of functional status, quality of life, emo- months followed by home training), several studies
tional status and endothelium function in comparison examined whether the FES method could be a useful
with placebo, while no adverse events were reported. replacement. Maillefert et al.16 reported for the first

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4 European Journal of Preventive Cardiology 0(00)

% mean change
150 142

130
112
110
85
90

70

50 FES

30 Placebo

4 6
10

–10
–8 –6
–11
–30 –21
–31
–50
DKCCQ-s DKCCQ-s DFMD DZung SDS DBDI

Figure 1. Mean per cent change in examined parameters in functional electrical stimulation (FES) and placebo groups.
KCCQ-s: Kansas City Cardiomyopathy Questionnaire-summary score; KCCQ-f: Kansas City Cardiomyopathy Questionnaire-func-
tional score; FMD: flow-mediated dilatation; Zung SDS: Zung Self-rating Depression Scale; BDI: Beck Depression Inventory.

time a significant improvement in peak oxygen con- may also be followed by lower rehospitalization rates,
sumption, anaerobic threshold and six-minute walking although this was not assessed by the present study.
distance and calf muscle volumes after a FES protocol The Zung SDS and BDI scores, evaluated herein,
in 14 patients with CHF. In a recent meta-analysis by screen both somatic and non-somatic depressive symp-
Smart et al.,2 FES was shown to be inferior to exercise toms. Although there is no evidence of mechanisms dir-
training but superior to placebo. The obvious patient ectly linking FES and emotional status improvement, it
population that could benefit from FES sessions is is a reasonable assumption that amelioration of func-
CHF patients who are unable to exercise due to tional status allows patients to overcome daily activity
NYHA class III/IV or coexisting medical conditions. limitations, which may be expressed by a perception of
In the present study, we have shown for the first time a better quality of life.
that FES benefits continue to occur in older age groups, Systemic vasoconstriction and endothelial dysfunc-
in which patients are more sedentary and more likely to tion are important pathophysiologic attributes in
be unable or unwilling to undergo aerobic exercise, irre- CHF.24,25 Endothelial dysfunction, as assessed by
spective of CHF aetiology or NYHA class. brachial artery FMD, is associated with increased mor-
Patients suffering from CHF often report feelings of tality risk in CHF patients of both ischemic and
anxiety and depression, which are inversely correlated non-ischemic aetiology.26 In the elderly, endothelial
with NYHA class and six-minute walking test, without dysfunction is more pronounced both due to poor-
an association with objective CHF parameters such as quality lifestyle choices, such as smoking or reduced
ejection fraction, natriuretic peptides and cardiac physical activity and due to reduced endothelial nitric
output.17 Emotional stress has been shown to adversely oxide synthase expression and action, accelerated nitric
affect both short- and long-term prognosis in CHF.18 oxide degradation, increased production of reactive
Hospitalized CHF patients suffering from depression oxygen species and other mechanisms.27,28 Aerobic
are probably more numerous than most clinicians sus- exercise has been shown to improve FMD, with studies
pect (35% to 70%), with depressive symptoms asso- showing that increased blood flow leads to an increased
ciated with a significant increase in the risk of both endothelial release of nitric oxide.29 FES has also been
mortality and readmission rate.19,20 Physical exercise shown to improve FMD in CHF patients,5,30 albeit less
training has been shown to improve emotional status than exercise. According to the present study, this
and quality of life in CHF.21 improvement seems to extend to CHF patients of a
The KCCQ questionnaire is a well-validated instru- more advanced age, although there is not enough
ment for assessing health-related quality of life.22 The data to suggest whether it has any causative relation
KCCQ scores have also been associated with clinical with improved exercise tolerance or is simply concur-
outcomes,23 thus the FES-induced favourable effect rently observed.

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Parissis et al. 5

This study is a preliminary evaluation of FES in a 7. Green CP, Porter CB, Bresnahan DR, et al. Development
rather small group of elderly CHF patients. Based on and evaluation of the Kansas City Cardiomyopathy
the encouraging results observed herein, FES warrants Questionnaire: A new health status measure for heart
further investigation in this particular CHF population failure. J Am Coll Cardiol 2000; 35: 1245–1255.
8. Zung WWK, Richards CB and Short MJ. Self-rating
with larger study groups. Additional investigations may
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comparison or in combination with conventional exer- erties of Beck Depression Inventory: Twenty-five years of
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In conclusion, FES seems to be safe and effective in 10. Arnold JM, Marchiori GE, Imrie JR, et al. Large artery
improving exercise capacity, quality of life, emotional function in patients with chronic heart failure. Studies of
stress and endothelial function in elderly CHF patients. brachial artery diameter and hemodynamics. Circulation
Thus, pending confirmation by larger trials, FES may 1991; 84: 2418–2425.
be considered an alternative mode of training in older 11. Corretti MC, Anderson TJ, Benjamin EJ, et al.
patients who are unable or unwilling to exercise, either Guidelines for the ultrasound assessment of endothelial-
dependent flow-mediated vasodilation of the brachial
as a ‘target’ therapy or as a ‘bridge’ to conventional
artery: A report of the International Brachial Artery
exercise. Reactivity Task Force. J Am Coll Cardiol 2002; 39:
257–265.
Funding 12. Santulli G, Ciccarelli M, Trimarco B, et al. Physical activ-
This research received no specific grant from any funding ity ameliorates cardiovascular health in elderly subjects:
agency in the public, commercial, or not-for-profit sectors. The functional role of the beta adrenergic system. Front
Physiol 2013; 4: 209.
Conflict of interest 13. Kitzman DW, Brubaker PH, Herrington DM, et al.
Effect of endurance exercise training on endothelial func-
The authors declare that there is no conflict of interest related
tion and arterial stiffness in older patients with heart fail-
to this work.
ure and preserved ejection fraction: A randomized,
controlled, single-blind trial. J Am Coll Cardiol 2013;
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