In-hospital electrical muscle stimulation for patients early after heart failure decompensation: results from a prospective randomised controlled pilot trial.

BACKGROUND: Electrical muscle stimulation (EMS) is being evaluated as a possible alternative to exercise training to improve functional capacity in severely deconditioned patients with heart failure (HF). However, there is insufficient data on delayed effects of EMS starting early after decompensation. The aim of this study was to determine the impact of a short inpatient EMS intervention in severely deconditioned patients with HF on functional capacity and quality of life (QoL) over a follow-up period of 1 month.
METHODS: This is a prospective randomised sham-controlled pilot study. 45 patients hospitalised for decompensated systolic HF (58% men, mean age 66.4±10.2 years) were randomised to EMS (n=22) or sham stimulation (n=23) of lower limbs starting within 3 days after admission. The intervention included 7-10 sessions lasting from 30 to 90 min. The 6-minute walking test distance (6-MWTD), Duke Activity Status Index (DASI) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were evaluated at baseline, discharge and after 1 month.
RESULTS: All patients completed the programme with good EMS tolerance. 37 patients were included in the final analysis. At discharge, 6-MWTD improved from 206,1±61,3 to 299.5±91 m, DASI from 12.1±5.6 to 18.3±7.2 and MLHFQ from 55.6±8.5 to 34.2±9 with EMS compared with smaller improvements in the sham group (p<0.05 for all). One month after discharge, improvements in the EMS group remained significant for MLHFQ (p=0.004) and DASI (p=0.042) and statistically non-significant for 6-MWTD compared with the sham group.
CONCLUSIONS: Short-term in-hospital EMS leads to improvements in functional capacity and QoL in selected patients early after HF decompensation that are retained over 1 month after discharge and therefore may serve as initial intervention to improve physical capacity or as a bridge to further conventional exercise training. Larger studies are required to evaluate individual responses to an early initiation of EMS in decompensated HF as well as long-term effects. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Electrical muscle stimulation (EMS) is a promising alternative to physical exercise training in severely deconditioned patients with heart failure.

Short-term in-hospital EMS leads to improvements in functional capacity and quality of life in selected patients early after heart failure decompensation.

Early initiation of EMS may be used as initial intervention to improve physical capacity or as a bridge to further conventional exercise training in severely deconditioned patients with heart failure.

Introduction

Heart failure (HF) is prevalent worldwide and is associated with poor prognosis. Risk factors for morbidity and mortality include exercise intolerance and reduced functional capacity. Aerobic exercise training is recommended for stable patients with HF to improve functional capacity and symptoms and to reduce the risk of HF hospitalisations.1 However, exercise training capabilities are limited in many patients with HF due to markedly reduced cardiac output and peripheral muscle wasting. According to the literature, electrical muscle stimulation (EMS) has the potential to serve as an alternative or as initial approach before conventional training modalities in patients with HF with severely impaired exercise tolerance.2–16 However, in the majority of studies effects of EMS have been studied in outpatients with stable moderate HF, while data on its short-term use in advanced stages of HF or in the acute care setting are scarce. Deferred effects of inpatient EMS are missing, although the transition of a patient from hospital to outpatient care is the most vulnerable period which bears a high risk for re-hospitalisation.

The aim of this study was to evaluate the impact of in-hospital EMS started early after HF decompensation on functional capacity and quality of life (QoL) at discharge and 1 month after discharge by using 6-minute walking test distance (6-MWTD), Duke Activity Status Index (DASI) and Minnesota Living with Heart Failure Questionnaire results (MLHFQ) as primary endpoints.

Methods

This is a prospective randomised sham-controlled pilot trial designed to investigate the impact of early initiation of short-term EMS in patients with HF presenting with decompensated systolic HF on functional capacity and QoL with a follow-up period of 1 month.

Study population

We consecutively screened a cohort of 202 patients with reduced ejection fraction (EF ≤40%) admitted for acutely decompensated HF to the Cardiology department of Moscow City Hospital № 7 (currently City Clinical Hospital named after S.S.Yudin) over a period of 2 years. Inclusion criteria were: (1) age ≥18 years (2) hospitalisation for acute decompensation of systolic chronic heart failure (CHF). Exclusion criteria were: (1) acute major cardiovascular events (acute coronary syndrome, cardiogenic shock, acute stroke, pulmonary embolism) (2) uncontrolled life-threatening ventricular arrhythmias, (3) indications for urgent cardiovascular surgery including severe valvular heart disease (4) recent deep vein thrombosis (5) leg skin lesions (ulcers, maceration, eczema etc) (6) extensive peripheral oedema impeding effective myostimulation (7) inability to perform 6-minute walking test (6-MWT) or to complete the questionnaires due to cardiac or non-cardiac conditions.

Forty-five patients were included in the study. Most common causes for non-inclusion were inability to perform 6-MWT due to severity of HF, refusal to participate in the study, impaired mental function, peripheral oedema and trophic skin changes.

The study protocol was conducted in accordance with the Declaration of Helsinki and the Consolidated Standards of Reporting Trials statement. Written informed consent was obtained from all the subjects and the protocol was approved by the local ethics committee. The patients could withdraw consent at any moment of the study. All patients received appropriate pharmacological therapy including loop diuretics, ACE inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists according to the most recent European Heart Failure guidelines at the time of the study (2016). In all patients, doses of the beta-blockers were maintained at the highest possible levels and/or up-titrated to the maximum tolerated dose.

Randomisation and blinding

The design of the study was experimental measuring the effects of EMS on physical tolerance and QoL in a sample of patients with CHF with reduced EF in a randomised sham-controlled manner. Patients who met the inclusion criteria were assigned in a 1:1 ratio either to effective EMS of leg muscles (group of intervention, n=22) or sham electric stimulation (group of control, n=23) by using the random number generator (Analysis ToolPak, Excel, Microsoft). In order to eliminate possible biases, examiners and interpreters for echocardiography, 6-MWT and questionnaires were blinded to the group allocation. The patients were instructed not to share any information about EMS sessions with the examiners. In addition, the doctor applying EMS to the patients was blinded from further analysis of the results until study completion.

Patient assessment

On admission, all patients underwent standard clinical examination, laboratory testing and transthoracic echocardiography (TTE). Within 3 days after admission, patients completed the baseline MLHFQ, the DASI questionnaire and performed a 6-MWT. All assessments other than TTE were repeated at the time of discharge from the hospital and 1 month after discharge.

Assessment of physical tolerance

6-MWT was conducted following the American Thoracic Society guidelines.17 Daily activity was assessed by the DASI, which is a self-assessment 12-item questionnaire for estimating functional capacity representing common aspects of physical function such as personal care, ambulation, household tasks, sexual life and recreation with respective metabolic costs.18 Ability to perform major activities was assessed with the final score ranging between 0 and 58.2 points (higher scores indicating better functional capacity).

QoL assessment

QoL was assessed by using the MLHFQ, consisting of 21 items rated on a 6-point Likert psychometric scale, representing how HF affects the physical and emotional aspects of QoL from 0 (none) to 5 (very much).19 MLHFQ provides a total score ranging between 0 and 105, from best to worst QoL.

Muscle stimulation

EMS was performed using a Stimul-01 electro-myostimulator developed by the Institute of Biomedical Problems, Russian Academy of Sciences and Biofizpribor Company. The setting including the placing of the electrodes is shown in figure 1. The EMS stimulator was originally developed for the space station as a means of prevention of muscle wasting caused by microgravity. The device generates bipolar symmetrical rectangular electrical impulses lasting 1±0.05 ms with a frequency of 25±1 Hz in the cyclic mode (1±0.1 s of stimulation and 2±0.1 s of rest). We used wetted non-adhesive electrodes that are positioned on the skin and fixed by special straps over the upper and lower portions of the muscle groups providing stimulation and contraction of the muscle mass between the electrodes. Anterior and posterior femoral and tibial muscles of both legs were stimulated simultaneously.

Figure 1

Position of the electrodes during electrical muscle stimulation

The intensity of stimulation in the EMS group was adjusted individually for each patient to achieve a visible muscle contraction followed by a gradual increase to attain maximum tolerable contraction. The stimulation intensity was adjusted at each session. In the sham group, the electrodes were positioned and fixed likewise and the stimulator switched on but minimal intensity was set not to cause any muscle contractions. Muscle stimulation procedures were performed 5 days a week. The duration of the first, second and third session was 30, 45 and 60 min in both groups with a maximum duration of the subsequent sessions of up to 90 min in the EMS group and 60 min in the sham group. Most patients were able to undergo 8 procedures in total before discharge with variations between 7 and 10 procedures. Average procedure time and the number of procedures did not differ significantly between groups (online supplemental figure 1).

Statistical analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences V.22 (IBM SPSS Statistics, USA). Sample size was calculated for detecting at least a 54 m difference in 6-MWTD and minimally important difference of 5 points for DASI and 10 points MLFHQ scores17–19 corresponding with changes in New York Heart Association class with a power of 80% and alpha risk of 5%. For this study, the sample size needed to achieve the calculated study power was 16 patients per group for 6-MWTD, 13 patients per group for DASI and 8 patients per group for MLHFQ.

Normality of distributions was tested with Shapiro-Wilk test. Continuous variables presented as mean value ±SD. T-test was used to compare the means of two groups. Categorical variables are shown as number and percentage and computed by using two-tailed Fischer’s exact test. Wilcoxon test was applied to determine the significance of difference in the linked samples. P value<0.05 was considered significant.

Results

All 45 patients completed the EMS or sham programme in the hospital. During the 1 month follow-up period, two patients assigned to EMS group dropped out of the study, one of them refused to attend the outpatient visits and one because of HF re-hospitalisation. Six patients assigned to the sham group did not complete the follow-up, three of them refused to attend and three had to be re-hospitalised with worsening of HF. There were no hospital readmissions during the 1 month of follow-up among patents which have been included in the final analysis.

The study flow chart is shown in figure 2.

Figure 2

Study flow chart. CHF, chronic heart failure; DASI, Duke Activity Status Index; EMS, electrical muscle stimulation; HF, heart failure; MLHFQ, Minnesota Living with Heart Failure Questionnaire; 6-MWT, 6-minute walking test.

There was no statistically significant difference between the two groups in regard to age, sex or reason for HF, left ventricular ejection fraction (LVEF), NYHA functional class, HF medications and comorbidities. 6-MWTD, DASI and MLHFQ scores at baseline were comparable between groups (table 1).

Table 1

Baseline clinical and demographic characteristics of study patients and EMS parameters

Patients’ characteristics	EMS (n=22)	Sham (n=23)	P value
Age (years)	64.5±11.0	68.9±9.0	ns
Male, n (%)	15 (68.2)	11 (47.8)	ns
Ischaemic CHF, n (%)	14 (63.6)	16 (69.5)	ns
Post MI	10 (45.5%)	11 (47.8%)	ns
h/o revascularisation (CABG/PCI)	8 (36.4%)	7 (30.4%)	ns
Arterial hypertension, n (%)	19 (86.4)	21 (91.3)	ns
Permanent atrial fibrillation n (%)	9 (41)	7 (30.4)	ns
Valvular heart disease, n (%)	4 (18.1)	3 (13.0)	ns
Diabetes mellitus, n (%)	5 (22.7)	7 (30.4)	ns
LVEF, %	32.3±3.5	30.8±6.1	ns
Average length of hospital stay, days	11.7±2.7	11.9±2.4	ns
NYHA class, n (%)(at the time of enrolment)IIIIV	17 (77.2)5 (22.7)	19 (82.6)4 (17.4)	ns
Loop diuretics, n (%)	22 (100)	23 (100)	ns
ACEi/ARBs, n (%)	20 (90.9)	22 (95.6)	ns
Beta-blockers, n (%)	20 (90.9)	19 (82.6)	ns
MRAs, n (%)	19 (86.4)	18 (78.3)	ns
Digoxin, n (%)	7 (31.8)	6 (26.1)	ns
Statins, n (%)	19 (86.4)	18 (78.3)	ns
CRT-P/CRT-D, n (%)	1 (4.5)	2 (8.7)	ns
ICD, n (%)	1 (4.5)	1 (4.3)	ns

ACEi, ACE inhibitors; ARBs, angiotensin receptor blockers; CABG, coronary artery bypass grafting; CHF, chronic heart failure; CRT-P/D, cardiac resynchronisation therapy (pacing/defibrillator); EMS, neuromuscular electrical stimulation; h/o, history of; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MRAs, mineralocorticoid/aldosterone receptor antagonists; ns, non-significant; NYHA, New York Heart Association; PCI, percutaneous coronary interventions.

Safety and tolerability

No significant acute changes of heart rate (Δ±20 b.p.m) and blood pressure (Δ±20 mm Hg) during EMS procedures were observed (thresholds according to Ref. 21). There were no adverse events requiring discontinuation of EMS procedures. Four patients reported mild muscle pain after the first sessions that resolved spontaneously. Two patients reported some mild-to-moderate general discomfort (most likely due to anxiety) without any alterations of vital signs throughout all EMS sessions which did not resolve with decreasing the stimulation intensity. However, none of the patients did discontinue the course of stimulation.

Functional capacity and QoL

At discharge, all measures of functional capacity and QoL improved significantly in the EMS group compared with the baseline values (table 2). In the sham group, the QoL, which was defined by a lower score on the MLHFQ, also improved significantly, while DASI and 6-MWTD demonstrated only a trend to improvement without reaching statistical significance (table 2). Patients who underwent EMS had significantly better scores of MLHFQ and DASI, as well as 6-MWTD compared with those in the sham group (figure 3).

Table 2

Changes in quality of life and functional status

Allocation	Parameter	Baseline	Discharge	1 month
EMS
	MLHFQ score	55.63±8.53	34.18±9.02*	37.77±7.25*
	DASI score	12.11±5.61	18.29±7.17*	17.51±4.59*
	6-MWTD, m	206.09±61.29	299.5±91.05*	284.63±83.17*
Sham
	MLHFQ score	56.47±7.11	48.73±8.09*	46.39±8.01*
	DASI score	11.60±3.75	13.37±4.32	14.39±4.11*
	6-MWTD, m	211.39±51.62	236.82±54.73	248.43±69.79*

*P<0.05—for difference between baseline and after procedures inside the groups.

DASI, Duke Activity Status Index; EMS, neuromuscular electrical stimulation; m, metres; MLHFQ, Minnesota Living with Heart Failure Questionnaire; 6-MWTD, 6-minute walking test distance.

Figure 3

Comparison of MLHFQ, DASI and 6-minute walking test distance between groups at baseline, discharge and 1 month of follow-up. Higher scores for MLHFQ indicate lesser quality of life. EMS, electrical muscle stimulation; DASI, Duke Activity Status Index; MLHFQ, Minnesota Living with Heart Failure Questionnaire; 6-MWT, 6-minute walking test.

One month after discharge, improvements in the EMS group remained significant for MLHFQ (p=0.004) and DASI (p=0.042) and statistically non-significant for 6-MWTD compared with smaller improvements in the sham group.

There was no meaningful difference in NYHA class and guideline based medical therapy between groups at 1 month after discharge.

Discussion

The main and new finding of this study is that short-term in-hospital EMS for patients early after HF decompensation by the time of discharge was able to generate beneficial effects on exercise tolerance, functional capacity and QoL of these patients that are retained over a follow-up period of 1 month. Our finding supports the concept of using EMS early after acute HF decompensation as a bridge to physical exercise training during periods of severe muscular deconditioning.

Previous studies related to EMS in HF mostly included outpatients in stable medical state.16 We enrolled patients at the latest 3 days after admission for HF decompensation. There are only limited data on the impact of EMS in patients hospitalised with advanced or acutely decompensated HF and its feasibility is still under investigation.20–24 However conventional training modalities are limited in these severely deconditioned patients. Moreover, prolonged immobilisation additionally contributes to skeletal muscle weakness in patients hospitalised for HF.25 A recent meta-analysis by Liu et al illustrates that EMS in critical patients prevents intensive care unit-acquired muscle weakness, shortens the length of stay in the hospital and may improve the ability to perform daily activities by the time of discharge.26 Thus, one can assume that similar effects of EMS can be achieved shortly after HF decompensation. High rates of hospital readmission for patients with HF reflect particular vulnerability of patients with HF early after discharge and may indicate low compliance to treatment including non-pharmacological measures such as physical activity.27–29 Through initial fitness improvement, EMS offers a bridge to conventional exercise or can be regarded as a substitute for physical training during the hospital-to-home transition period. Even more important, early initiation of EMS may prevent additional muscle wasting during hospitalisation in patients with HF with high prevalence of sarcopenia and frailty and may also increase their acceptance of recommendations for cardiac rehabilitation.30–32

In our study, even a short-term EMS course was sufficient to increase 6-MWTD and to improve QoL corresponding with previous reports.20–22 Immediate beneficial effects of EMS are observed even after a single session which might partly be explained by peripheral vasodilation and better muscle perfusion.22 33 Likewise, healthy subjects demonstrate changes in inflammatory cytokines similar to the effects of active exercise after only 30 min of EMS.34 To our surprise, there was no significant difference in 6-MWTD between the two groups in our study after 1 month. It may be argued that patients from the sham group had to increase their level of daily activity after discharge anyway bringing them closer to the patients from the EMS group in terms of physical tolerance. Another explanation my be that individual differences between patients have generally an important impact on results in studies with small sample sizes.

The impact of a particular EMS stimulation protocol on outcome is largely unknown. Various stimulation parameters and protocols have been used previously in mainly small studies. Most of the protocols involved prolonged EMS courses of up to 5–8 weeks.2 Unfortunately, no reliable data are available comparing different methods of EMS application. Short-term and long-term effects of EMS may vary depending on the regimen and the duration of the course. Nuhr showed that chronic low frequency stimulation induced a shift in the muscle fibre type from fast glycolytic to slow oxidative fibres.10 Small earlier trials found that high frequency EMS produced improvements in muscle strength and metabolic measures of exercise capacity in highly selected patients and found that higher frequency stimulation normally used for muscle strengthening was not suitable to produce a sustained increase in oxygen uptake. Instead, very low frequencies were preferable probably because of lesser fatigue of the type I oxidative muscle fibres, even in severely deconditioned patients with HF.35 Finally, we know at least from one study, that there was no beneficial effect by adding EMS to conventional exercise training in HF.36 37 Our study shows beneficial effects of low-intensity stimulation on exercise capacity, whereas evaluation of changes in strength was not part of this investigation. In our protocol, low-intensity EMS allowed simultaneous stimulation of both anterior and posterior muscle groups for a longer period of time. In comparison to previous studies, our protocol allowed to involve a larger number of muscle groups during a session leading to simultaneous effective contraction of anterior muscles as opposed to contracting posterior muscle groups and vice versa. EMS regimen with counteraction of opposite muscle groups stretched against each other markedly improves the benefits of the procedures. Focus on a larger amount of stimulated muscle groups is known to increase efficacy of EMS regardless of the duration of the procedures.38 This may at least partially explain why even eight EMS sessions in average were enough to provide beneficial effects in our study.

Limitations

We recognise several limitations in our study. We enrolled a relatively small number of patients with a limited follow-up time, which may reduce the power of the study. However, according to most recent evidence this is a common limitation for all studies with EMS in patients with HF of similar disease severity with a crude number of 10–15 patients for each group on average.2 24 39 Thus, our results provide some additional information to the knowledge gap. The high percentage of non-inclusion due to common real-life causes in a relatively large cohort of screened patients with HF does not eliminate certain selection bias. Larger studies are required to evaluate individual responses to an early initiation of EMS in decompensated HF as well as long-term effects. Although it was a randomised study, response to HF treatment could vary between individuals with potential impact on the level of improvements of functional status and QoL. Levels of brain natriuretic peptide (BNP) were not investigated based on limited real-life facilities of the city community hospital where the study was conducted. However, according to the most recent guidelines BNP is still not required for diagnosing of heart failure with reduced ejection fraction (HFrEF) in case of low LVEF and obvious clinical signs and symptoms of HF. Only a relatively small percentage of our patients had implanted devices mainly due to economic limitations. At the time of the study, neither sacubitril/valsartan, nor SGLT2 inhibitors were widely implemented in the patients with HFrEF. Fully blinding was not possible due to differences in subjective perception of effective EMS and sham procedures by the patients. Physical tolerance was not evaluated with more precise methods such as cardiopulmonary exercise testing because of the disease severity in these patients. Activity of daily living after discharge was measured only by DASI score without using more definitive modalities like accelerometry.

Conclusion

Short-term in-hospital EMS early after HF decompensation has beneficial immediate effects on functional capacity and QoL that are maintained at 1 month after discharge. In selected patients with HF, EMS may be considered as initial intervention for patients who are unable to exercise, either as a substitute or as a bridge to conventional exercise training. Further studies are needed to explore the full potential of early EMS under these circumstances.