†These authors contributed equally.
Academic Editors: Kazuhiro P. Izawa and Peter H. Brubaker
Background: Aerobic exercise, either continuous or high intensity
interval training (HIIT), induces important benefits in chronic heart failure
(CHF) patients. Resistance training has been also shown to be beneficial in CHF.
However, data regarding combined aerobic exercise and muscle strength training is
still limited. The aim of this study was to investigate whether adding strength
training to a HIIT protocol within a cardiac rehabilitation (CR) program has a
cumulative beneficial effect on the functional capacity (FC) and quality of life
(QoL) in patients with CHF. Methods: Forty-four consecutive patients [35
males, ejection fraction (EF)
Chronic heart failure (CHF) is a clinical syndrome that remains the leading cause of mortality and morbidity worldwide [1, 2]. Its prevalence, according to the 2021 American Heart Association Statistical Update, is estimated at approximately 1.8% of the total US population and between 1% and 2% in Europe [3, 4]. CHF is characterized by impaired microcirculation [5, 6, 7, 8], vascular endothelial dysfunction [5, 6, 7, 8], exercise intolerance, reduced exercise capacity [9, 10, 11, 12], and reduced skeletal muscle mass [13, 14, 15, 16]. The effect and symptoms of CHF on individuals’ everyday routines are reflected in their health-related quality of life (QoL), which is usually decreased in these patients [17, 18].
During the last decades, studies investigating aerobic exercise are shown to improve microcirculation [19, 20] and vascular endothelial function [21, 22, 23], exercise capacity [21, 22, 23, 24, 25, 26], skeletal myopathy [19, 27, 28], and QoL [25, 29, 30] in CHF patients. The most recent 2021 European guidelines for managing and treating chronic heart failure, include a class IA recommendation for patients with CHF to engage in regular aerobic exercise protocols which are the most studied aspects of cardiac rehabilitation (CR) programs [31].
Data in the last two decades suggests high intensity interval training (HIIT) to induce at least comparable benefits to continuous regimes and also provides evidence on the benefits of combined aerobic and resistance exercise training protocols in CHF patients [32, 33, 34, 35, 36, 37, 38]. Combined regimes have been shown to induce additional benefits in terms of strength and aerobic variables [28, 39, 40, 41, 42], and therefore, resistance/strength training has been established as core component of cardiac rehabilitation in chronic heart failure [43, 44, 45, 46]. However, extending previous findings regarding the combination of HIIT and resistance regimes in heart failure, and adding new knowledge in literature, would be useful for the establishment of individualized exercise training programs.
We hypothesized that the addition of strength training to HIIT may provide further improvement in strength and exercise capacity in CHF patients. Thus, the aim of this study was to investigate whether adding strength training to a HIIT protocol has a cumulative beneficial effect on the functional capacity (FC) and muscle function indices, as well as on the QoL, in patients with CHF undergoing a CR program.
Forty-four consecutive patients (35 males) with stable CHF under medication were
recruited in the CR program. Inclusion criteria were: (i) New York Heart
Association (NYHA) class II/III, (ii) age
Flow chart describing the process of the randomized clinical trial. LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; HIIT, high-intensity interval training; COM, combined training; Follow up, the period during the 36-session exercise training program.
This single-blinded, clinical randomized control study was performed between September 2015 and August 2019. It was approved by the Ethics Committee and the Administration Board of the hospital and it was in accordance with the Declaration of Helsinki. The study was registered in ClinicalTrials.gov with number NCT02387411. The CR program was a 3-month program consisting of 36 exercise training sessions, which were held three times a week. All patients from both groups performed 36 sessions in order to be included in the analysis.
All participants were asked to sign an informed consent. Patients were referred by outpatient HF departments of the biggest hospitals of the city. To determine their suitability for the program, including safety and feasibility of exercise, expert cardiologists evaluated their medical history, as well as laboratory and imaging exams, and performed clinical examination of the patients. Each patient underwent a symptom-limited maximal CPET on an electromagnetically braked cycle ergometer (Ergoline 800; SensorMedics Corporation, Anaheim, CA, USA) twice; before and after the CR program.
Individual work rate increments were calculated for an 8–12-minute test
duration [47] at baseline and at the end of the rehabilitation program in each
patient. During CPET, patients could breathe using a special mask with a
low-resistance valve and an established gas mixture. While breathing, various
breathing parameters including oxygen uptake (VO
Strength training assessment was performed by the one-repetition maximum (1RM) test at the beginning and the end of the CR program in all participants. The 1RM test measured each patient’s ability to lift the maximum weight in one repetition. Additionally, muscular endurance test, defined as the maximum number of repetitions at 65% of the weight achieved in the 1RM test, was also recorded. There was always a familiarization day before the test day of the 1RM. The 1RM test was performed the same day with the muscular endurance test. Patients had enough time between the tests in order to recover.
Using stratified randomization, patients were randomly allocated in 2 different
exercise training groups; either the HIIT or the high-intensity interval training
(HIIT) group combined with muscle strength training (COM). The appropriate
intensity in watts (W) of each patient’s workout session was structured according
to the outcomes of their preliminary CPET. Patients were randomized for age
(cut-off point: 50 years) and peak VO
The total duration of each session, as well as the aerobic exercise program, was
similar in both groups. Specifically, HIIT was a modified Wisløff’s protocol
[38]. All patients performed a 7-minute warm-up on a stationary bike (Ironman M3
Upright Cycle, Keys Fitness Products, LP. Garland, Texas 75041, USA) at 45% of
their peak VO
The main difference between HIIT and combined with strength training (COM) groups was that, at the end of the aerobic exercise, patients of the HIIT group performed balance and coordination exercises including narrow corridor walking, backward narrow corridor walking and side walking in both sides, while patients of the COM group performed resistance training according to the 1RM test including strength exercises for the quadriceps (knee extension), leg curl (knee flexion) and the chest muscles (shoulders flexion & chest press). Strength exercises were initially prescribed to 60% of the 1RM test and then gradually increased in number of repetitions and weight (2–3 sets of 10–12 repetitions between 60%–75% of the 1RM) with 1-minute rest period between sets.
Blood pressure, oxygen saturation and heart rate were measured throughout the session and dyspnea or fatigue was assessed by the Borg scale.
Quality of life was evaluated using the validated Greek version of the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) [48], a disease-specific questionnaire originally developed by Rector et al. [49] for systematic and comprehensive assessment of patients’ perception of the effects of HF and its management on their daily life. This tool for measuring the functional status of patients with HF includes 21 items consisting of 8 items on physical aspects, 6 on emotional aspects, and 7 other items adding up to the total score that cover socioeconomic and other issues related to HF. The response score ranges from 0–105 points, with higher scores indicating higher severity and, therefore, lower QoL due to HF symptoms.
MLWHF questionnaire was given to each patient prior the start and at the end of the CR program. Patients were given enough time, space and privacy to complete the questionnaire.
Primary outcomes of our study were (i) aerobic exercise capacity, including peak
VO
A power analysis was performed before the initiation of the study, based on
previous studies with similar methodology that investigated the improvement in
aerobic exercise capacity, through peak VO
Normality of distribution was checked with the Shapiro-Wilk test. Variables are
expressed as mean
Demographics and CPET indexes of total sample and within each exercise training group are demonstrated in Table 1 HIIT and COM groups had similar baseline values before the CR program. Patients of both exercise training groups usually reached 13–15 in Borg scale during maximal exercise. HIIT was mostly at 13–14 while COM at 14–15. However, there were no significant differences between groups.
Demographic characteristics* | All patients | HIIT group | COM group | |
Number of patients (N) | 44 | 19 | 25 | |
Gender (Males/Females) | 35/9 | 16/3 | 19/6 | |
Age (years) |
56 |
54 |
57 | |
Height (cm) |
175.2 |
176.1 |
174.4 | |
Weight (kg) |
89.1 |
92.2 |
86.3 | |
BMI (kg/m |
28.7 |
29.4 |
28.1 | |
NYHA stage (class II/III) | 34/10 | 14/5 | 20/5 | |
EF before rehabilitation (%) |
30 (28–40) | 35 (30–42.5) | 30 (25–35) | |
Type of CHF | ||||
Dilated cardiomyopathy [n (%)] | 12 (27.3%) | 4 (21%) | 8 (32%) | |
Ischemic [n (%)] | 24 (54.5%) | 11 (58%) | 13 (52%) | |
Other (valvopathy, etc.) [n (%)] | 8 (18.2%) | 4 (21%) | 4 (16%) | |
Medication | ||||
Diuretics [n (%)] | 29 (66%) | 12 (63%) | 17 (68%) | |
ACE inhibitors [n (%)] | 22 (50%) | 10 (53%) | 12 (48%) | |
ARBs [n (%)] | 5 (11%) | 4 (21%) | 1 (4%) | |
b Blockers [n (%)] | 43 (98%) | 19 (100%) | 24 (96%) | |
Aldosterone Antagonists [n (%)] | 32 (73%) | 14 (74%) | 18 (72%) | |
Ca blockers [n (%)] | 1 (2%) | 0 (0%) | 1 (4%) | |
Vasodilators [n (%)] | 2 (5%) | 1 (5%) | 1 (4%) | |
Digoxin [n (%)] | 3 (7%) | 0 (0%) | 3 (12%) | |
Amiodarone [n (%)] | 6 (14%) | 3 (16%) | 3 (12%) | |
Cardiopulmonary exercise testing and muscular indexes before rehabilitation* | ||||
Rest VO |
4.7 |
4.7 |
4.7 | |
Peak VO |
18.4 |
18.4 |
18.5 | |
Peak predicted VO |
64 |
62.2 |
65.4 | |
VE/VCO |
29 |
28.5 |
29.4 | |
Peak WR (watts) |
101 |
103.6 |
99 | |
Relative peak WR (watts/kg of body weight) |
1.14 |
1.15 |
1.14 | |
WR at AT (watts) |
42.9 |
46.1 |
40.5 | |
Relative WR at AT (watts/kg of body weight) |
0.49 |
0.52 |
0.47 | |
1RM quadriceps (kg) |
42 (30–53) | 47 (28–52) | 40 (31–54) | |
Relative 1RM quadriceps (kg/kg of body weight) |
0.49 (0.37–0.57) | 0.51 (0.35–0.59) | 0.47 (0.41–0.55) | |
1RM chest muscles (kg) |
50 (35–70) | 60 (45–75) | 45 (28–68) | |
Relative 1RM chest muscles (kg/kg of body weight) |
0.60 (0.42–0.79) | 0.75 (0.48–0.82) | 0.56 (0.40–0.70) | |
Muscular endurance quadriceps (repetitions) |
10 (8–12) | 10 (7–13) | 10 (8–11) | |
Muscular endurance chest muscles (repetitions) |
12 (10–16) | 12 (10–16) | 11 (10–16) | |
BMI, body mass index; HIIT group, high-intensity interval
exercise group; COM group, HIIT combined with muscle strength exercise group;
NYHA, New York Heart Association; CHF, chronic heart failure; ACE,
angiotensin-converting-enzyme; ARB, angiotensin II receptor blockers; VO |
As far as the total number of CHF patients is concerned, the cardiac
rehabilitation program had beneficial effects on their functional capacity,
quality of life and ejection fraction. Most specifically, most CPET indexes
including peak VO
The beneficial effect of the CR program was also shown within each exercise
training group. Patients in HIIT group improved rest VO
Variables of the CR program | HIIT group (19 patients) | COM group (25 patients) | p value between groups | |||||
Before CR | After CR | p value* | Before CR | After CR | p value* | |||
Minnesota living with heart failure quality of life questionnaire | ||||||||
Physical score (units) | 11 (5–25) | 9 (2–16) | 0.020 | 10 (5–21) | 5 (2–9) | 0.001 | 0.962 | |
Emotional score (units) | 7 (3–14) | 4 (1–9) | 0.131 | 5 (2–9) | 3 (1–8) | 0.188 | 0.557 | |
Total score (units) | 33 (16–49) | 21 (7–31) | 0.017 | 23 (13–46) | 12 (7–24) | 0.004 | 0.704 | |
1 Repetition maximum test | ||||||||
Quadriceps (kg) | 47 (28–52) | 57 (47–65) | 40 (31–54) | 52 (34–63) | 0.785 | |||
Relative 1RM quadriceps (kg/kg of body weight) | 0.51 (0.35–0.59) | 0.60 (0.48–0.72) | 0.47 (0.41–0.55) | 0.55 (0.49–0.71) | 0.767 | |||
Chest muscles (kg) | 60 (45–75) | 65 (50–85) | 0.006 | 45 (28–68) | 55 (41–88) | 0.039 | ||
Relative 1RM chest muscles (kg/kg of body weight) | 0.75 (0.48–0.82) | 0.79 (0.56–0.91) | 0.007 | 0.56 (0.40–0.70) | 0.71 (0.57–0.88) | 0.021 | ||
Muscular endurance | ||||||||
Quadriceps (repetitions) | 10 (7–13) | 15 (10–20) | 10 (8–11) | 13 (12–15) | 0.294 | |||
Chest muscles (repetitions) | 12 (10–16) | 17 (12–20) | 11 (10–16) | 19 (15–26) | 0.002 | |||
Cardiopulmonary exercise testing indexes | ||||||||
Rest VO |
4.7 |
4.1 |
0.025 | 4.7 |
4.5 |
0.518 | 0.312 | |
Peak VO |
18.4 |
21.5 |
0.011 | 18.5 |
20.1 |
0.071 | 0.290 | |
Predicted peak VO |
62.2 |
73.6 |
0.006 | 65.4 |
72.2 |
0.028 | 0.322 | |
VE/VCO |
28.5 |
26.4 |
0.101 | 29.4 |
28.6 |
0.260 | 0.380 | |
AT (mL/kg/min) | 12.1 |
12.9 |
0.093 | 11.7 |
13.7 |
0.003 | 0.101 | |
Peak WR (watts) | 103.6 |
122.2 |
99.0 |
119.1 |
0.811 | |||
Relative peak WR (watts/kg of body weight) | 1.15 |
1.35 |
1.14 |
1.36 |
0.704 | |||
RQ/RER | 1.3 |
1.2 |
0.344 | 1.2 |
1.1 |
0.383 | 0.462 | |
Peak VE (L/min) | 46.3 |
62.9 |
53.1 |
70.5 |
0.861 | |||
WR at AT (watts) | 46.1 |
65.8 |
40.5 |
69.8 |
0.023 | |||
Relative WR at AT (watts/kg of body weight) | 0.52 |
0.74 |
0.47 |
0.80 |
0.002 | |||
Peak P |
39.8 |
33.7 |
0.007 | 34.8 |
33.5 |
0.400 | 0.062 | |
Ultrasound indexes | ||||||||
Ejection fraction (%) | 35 (30–42) | 35 (30–45) | 0.004 | 30 (25–35) | 35 (30–40) | 0.001 | 0.587 | |
AT, anaerobic threshold; HIIT group, high-intensity interval exercise group; COM
group, HIIT combined with muscle strength exercise group; CR, cardiac
rehabilitation; Rest VO |
It has been previously shown that aerobic exercise training, and spesifically HIIT, has a positive impact on functional capacity, muscular endurance, and QoL in CHF patients. This study demonstrated that the addition of muscle strength training to a HIIT protocol (COM) results in improved workload at the anaerobic threshold and better performance in the 1RM and muscular endurance test of the chest muscles in CHF patients. Overall, it appears that COM has some advantages regarding aerobic capacity and muscle strength improvement when compared to HIIT protocol. However, the comparison between HIIT and COM regarding other indices of CPET and quality of life, revealed similar improvements in both groups, suggesting that the addition of strength training to HIIT may not have a cumulative beneficial effect.
During the last decades, many studies have evaluated the effect of HIIT on functional capacity, microcirculation, vascular endothelial and skeletal muscle function, and QoL in CHF patients, demonstrating beneficial effects on most of these parameters [19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42]. Moreover, the superior effects of HIIT protocols in CHF patients undergoing rehabilitation compared to continuous or moderate aerobic training have been also shown [28, 32, 33, 34, 35, 36]. However, data regarding the effects of combined exercise training protocols such as HIIT with strength training is limited in literature. There are only a few studies that compared HIIT versus HIIT and muscle strength training in order to evaluate the impact of the addition of resistant training (RT) on functional capacity, physical performance and QoL [24, 28, 39, 40, 41, 42].
Specifically, Bouchla et al. [28] investigated the additional effects
of strength training on muscle strength, functional capacity and body composition
in CHF patients participating in an interval aerobic training program. They
showed a greater improvement in the combined training than in the aerobic
training group regarding the 2RM test. However, there was no difference in total
lean mass, total fat mass, leg lean mass, leg fat mass, and CPET indices such as
peak VO
Some of our findings may differ compared to the results of previous studies, as we observed significant improvements in the work rate at AT, the 1RM test and muscular endurance of the chest muscles and we did not manage to demonstrate differences in other CPET or QoL indices. A possible explanation of these differences is that, in the present study, we used exercise protocols characterized by different intensity, workload, active recovery intervals and types of RT compared with the previous studies. Moreover, our patients had already good functional capacity at baseline, being of low or intermediate HF severity. It is worth mentioning that our study evaluated another significant parameter, EF. We found that EF improved within each exercise training group after the CR program.
In this study, we examined all aspects of the MLWHF questionnaire (physical, emotional, and total scores) revealing that patients improved in physical and total score in both groups. However, the emotional aspect didn’t improve in either group despite the beneficial effects of exercise training on the patients’ cardiovascular system and functional capacity. This may suggest that further psychological evaluation is needed at baseline and during the exercise training program, as psychopathological symptoms, such as anxiety or depression, are common in CHF patients [50, 51].
Aerobic and resistance exercise training result in beneficial effects on
skeletal muscles, inducing skeletal muscle hypertrophy, reversal of the altered
muscle fiber composition and increase in mitochondrial and capillary density in
CHF patients [19, 40, 52]. Indeed, in the present study, patients in both HIIT
and COM exercise training groups improved their strength indexes, including the
1RM test and muscular endurance. In addition, the comparison between HIIT and COM
revealed improvements in the upper extremities muscle function indexes (1RM and
muscular endurance) in favor of the COM group. However, we did not observe
differences in the lower extremities muscle function. This finding could be
explained by the fact that patients of both group performed cycling exercise
training, which might have improved skeletal myopathy in a similar way in both
HIIT and COM groups. The improvement in muscular strength of the lower limbs and
exercise tolerance in patients of both groups might be associated with the
exercise-induced increase in oxygen extraction and the improvement of peak
VO
Finally, as far as safety of a cardiopulmonary rehabilitation program is concerned, there is a previous study by Ellingsen Ø et al. [53] where authors reported 9 severe cardiovascular and 6 non-cardiovascular events during the exercise training program, as well as 19 severe cardiovascular and 3 non-cardiovascular events at follow-up within the first year. Among cardiovascular events, 2 were fatal at follow-up while none of them was fatal during the program. Among non-cardiovascular events, there was 1 fatal event at follow-up and no fatal events during exercise. It is also noteworthy that the majority of adverse events happened in patients who underwent HIIT (39%) compared to moderate continuous training (34%) and recommended regular exercise (25%). In our study, no severe cardiovascular or non-cardiovascular adverse events during our rehabilitation program were observed. Rehospitalizations due to non-cardiovascular events occurred in 3 patients out of the 44 of our study at 1-year follow-up. In most studies in literature, HIIT has been shown to be safe and feasible in patients with HF and other populations [54, 55, 56, 57]. Moreover, combined training, and specifically resistance training after HIIT or moderate intensity continuous training, has also been proven to be feasible, even in untrained older adults [58]. In our study, all patients of the COM group successfully completed resistance training after HIIT in each session. Consequently, combined exercise training regimes seem to be feasible and safe in patients with heart failure and reduced or mildly-reduced ejection fraction.
There are some important limitations. The small number of the study participants might have led to underpowered comparisons between groups for some indices that did not allow revealing additional possible benefits of COM in the parameters of interest.
Our study presented the beneficial effects of muscle strength training in combination with HIIT-based aerobic exercise training. Although randomized controlled studies combining RT and HIIT and including larger numbers of CHF patients are required in order to reveal potentially more beneficial effects of exercise training on functional ca-pacity and vascular endothelial function of those patients, the addition of individualized RT to aerobic exercise should be included in cardiac rehabilitation programs of CHF patients. RT has been found to improve skeletal muscle mass and function, and reverse skeletal myopathy [19, 27, 28] which are both characteristics in heart failure, leading in reduced functional capacity and poor QoL. We supposed that the increase in the 1RM test and in muscular endurance, even in the chest muscles only, may contribute to the reverse of skeletal myopathy which, in our opinion, is one of the most important issues in HF. On the other hand, patients performing HIIT alone may improve their balance compared to COM, which may also be important aspect in HF. However, this was not a parameter of interest in our study and, unfortunately, we did not compare it between the 2 groups. Finally, the addition of other exercise interventions to the HIIT and RT exercise protocols, such as breathing exercises and inspiratory muscle training might be also an interesting field for future research focusing on the exercise-induced functional and clinical adaptations in CHF patients.
The addition of muscle strength training to a HIIT protocol resulted in better workload at the AT, as well as in improvement of the 1RM test and muscular endurance of the chest muscles in CHF patients. Our findings further suggest that implementing resistance training in HIIT protocols within the CR programs may result in greater exercise-induced benefits. Improvements in muscular function parameters such as the 1RM test and muscular endurance, may improve skeletal myopathy of CHF patients leading, thus, in better functional capacity and improved QoL. However, further studies are required to uncover potential mechanisms of exercise-induced beneficial adaptations in patients with heart failure.
CR, cardiac rehabilitation; HIIT group, high-intensity interval exercise group;
COM group, HIIT combined with muscle strength exercise group; NYHA, New York
Heart Association; CHF, chronic heart failure; ACE,
angiotensin-converting-enzyme; ARB, angiotensin II receptor blockers; VCO
The data that support the findings of this study are available on request from the corresponding author [MA]. The data are not puplically available due to their containing information that could compromise the privacy of research participants.
DS, SN, EK and AP designed the research study and revised the manuscript; MA, CK and DD performed the research and extracting data; SD and NR provided help and advice on data acquision; CK analyzed the data; MA and CK drafting and writing the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
The study was conducted in accordance with the Declaration of Helsinki, and approved by the In-stitutional Review Board of Evangelismos Hospital (protocol code: 236, date of approval: 27-11-2015). Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patients to publish this paper.
We would like to thank all the members of Clinical Ergospirometry, Exercise & Rehabilitation Labor-atory of Evangelismos Hospital for their valuable help. Open Access funding provided by the Qatar National Library.
This research received no external funding.
The authors declare no conflict of interest. Despina Sanoudou is serving as one of the Editorial Board members of this journal. We declare that Despina Sanoudou had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Kazuhiro P. Izawa and Peter H. Brubaker.
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