Background
Chronic heart failure is a clinical syndrome “caused by structural and/or functional cardiac abnormality, resulting in a reduced cardiac output” [
1]. Based on the measurement of the ejection fraction, it can be distinguished between heart failure with reduced (< 40%), mid-range (40–49%), and preserved ejection fraction (≥50%) [
1]. Heart failure with reduced ejection fraction occurs less often than heart failure with preserved ejection fraction and men are more affected than women [
2]. In 2016, the disease was the second most common cause for hospital admission in Germany, whereby in more than 80% of all cases patients were older than 70 years [
3]. The most recent European data present that 12-month all-cause mortality rates for patients with chronic heart failure were up to 17.4% [
4]. Additionally, in 2012, costs for the disease in the USA were 30.7 trillion USD, which is predicted to increase by 127% by the year 2030 [
5].
For the treatment of chronic heart failure, it is essential to accomplish valid diagnostic and therapeutic methods. Considering diagnostic methods, blood, electrocardiography, echocardiography, and maximum oxygen uptake are established measures [
1,
6]. However, maximum oxygen uptake underlies various central and peripheral factors such as stroke volume, cardiac output, cardiac power output, and arteriovenous oxygen difference, respectively [
7,
8]. In recent years, cardiac power output gained more importance, because of its possible superior prognostic impact compared to maximum oxygen uptake in patients with chronic heart failure [
9‐
11]. Since it is a systemic disease, it also affects the peripheral system of the patients [
12]. In fact, peripheral changes such as decreased skeletal muscle perfusion and mitochondrial dysfunctions in patients with chronic heart failure are partially seen as the main reason for a reduced performance during exercise [
13,
14]. Additionally, the disease is characterized by a high heterogeneity especially affecting etiology and pathogenesis [
15,
16]. As a consequence, factors underlying maximum oxygen uptake could differ between patients with chronic heart failure and thus cannot be generalized. Still, the aforementioned central and peripheral factors are often insufficiently addressed, because they are usually measured invasively [
17]. Especially taken the importance of the cardiac power output and peripheral changes into account [
9‐
11,
13,
14], it is promising to assess central and peripheral factors of oxygen uptake by recent non-invasive technologies such as bioreactance analysis and near-infrared spectroscopy [
10,
17‐
19].
In this context, previous studies investigating patients with chronic heart failure have focused on stroke volume [
20], cardiac output [
10,
11,
20], and cardiac power output [
10,
11]. Other studies examined healthy participants on stroke volume, cardiac output [
21], and cardiac power output [
22]. To get more insights into peripheral changes, two studies investigated isokinetic and isometric peak torque of the knee in patients with heart failure [
23] and healthy participants [
24], respectively. Overall, the studies show that patients with chronic heart failure have lower values of up to 45.8% in central factors and up to 35.3% in peripheral factors compared to separately investigated healthy participants. However, all previous studies only investigated either patients with chronic heart failure or healthy participants by different settings, questioning the validity of the described differences. Thus, for allowing stronger conclusions, more research comparing both groups by the same research design is needed.
To our knowledge, there is only one study that has compared the cardiac output between patients with chronic heart failure and healthy controls [
25]. In this study, patients with chronic heart failure had a 32.9% lower cardiac output than healthy controls. Furthermore, regarding the known reduced oxidative capacity of the entire muscular system in patients with chronic heart failure [
26], there is only one study that has investigated differences between the aforementioned groups [
19]. The results showed no significant group differences in tissue oxygen saturation of the vastus lateralis muscle by a cycling ergometer. However, testing was carried out on a submaximal level. As maximum oxygen uptake is the gold standard for risk stratification of chronic heart failure [
6], it is reasonable to investigate central and peripheral factors at maximum level as well. Taken together, while there are few studies that investigated central factors of maximum oxygen uptake in both groups by the same research design revealing significant differences, peripheral factors at maximum load are not investigated, yet.
The aim of this study was to compare non-invasively measured central and peripheral factors of oxygen uptake between patients with chronic heart failure and healthy controls. Based on previous research [
19,
25], we hypothesize that patients with chronic heart failure show lower values in both central and peripheral factors than healthy controls. Our findings will increase the understanding of underlying factors of oxygen uptake in patients with chronic heart failure, which will help in diagnosis and therapy.
Discussion
For the first time, we investigated non-invasively measured central and peripheral factors of oxygen uptake between patients with chronic heart failure and healthy controls by the same standardized research design. Our main findings were: patients with chronic heart failure had (a) a lower maximum oxygen uptake, (b) a similar cardiac output and cardiac power output at maximum oxygen uptake, and (c) lower values in muscle oxygen saturation of vastus lateralis muscle at rest and higher values at maximum load as well as lower values in isometric peak torque values.
Regarding our first main finding, patients with chronic heart failure had a most likely lower maximum oxygen uptake than healthy controls (Table
1). The maximum oxygen uptake of the patients was 15.6 ± 3.0 ml/kg/min, whereas healthy controls had 28.0 ± 2.1 ml/kg/min (− 44.3%). Previous studies support these findings: 15.4 ± 4.9 vs. 23.1 ± 3.0 ml/kg/min (− 33.3%) [
18], 15.2 ± 1.1 vs. 21.1 ± 1.7 ml/kg/min (− 28.0%) [
25], and 20.1 ± 6.0 vs. 33.3 ± 7.0 ml/kg/min (− 39.6%) [
19]. This outcome reinforces the well-known negative impact of chronic heart failure on maximum oxygen uptake and performance capacity. These differences may be due to several underlying central and peripheral factors. However, solely based on this finding, it is not possible to conclude whether the lower maximum oxygen uptake is primarily impacted by central and/or peripheral factors. Regardless of the potential multifactorial reasons for a lower maximum oxygen uptake, it is still an established parameter for the risk stratification of chronic heart failure [
6].
Concerning our second main finding, patients with chronic heart failure had a similar cardiac output and cardiac power output at maximum load compared to healthy controls (Fig.
3). Our results showed a cardiac output for patients and healthy controls of 15.0 ± 1.4 and 15.1 ± 1.3 l/min (− 0.7%), respectively. Values for cardiac power output for patient and healthy controls were 3.8 ± 0.3 and 4.0 ± 0.3 (− 5.0%), respectively. In contrast, previous studies showed lower values of up to 31.0% in cardiac output [
10,
11,
20,
21] and up to 45.8% in cardiac power output [
10,
11,
22] for patients with chronic heart failure compared to separately measured healthy participants. One possible explanation for these inconsistencies may be the different research designs and the high intra- and interindividual variabilities of the patients with chronic heart failure (Figs.
2 and
3) [
15]. Considering that, during load, patients had a lower heart rate but higher stroke volume, our results for cardiac output are plausible. A rational explanation may be that the patients were very well medicated and based on the Kansas City Cardiomyopathy Questionnaire in a well general state. Nevertheless, additional information of the contractile reserve could have been meaningful to clarify our observations [
46]. Regarding the risk stratification of chronic heart failure, maximum oxygen uptake is the established gold standard [
6]. However, our results show that maximum oxygen uptake reveals little of the actual cardiac performance of patients with chronic heart failure as there are unclear differences in cardiac output and cardiac power output between both groups. These findings show that the cardiac power output may be suited better for estimating the cardiac performance of patients with chronic heart failure [
9‐
11].
Regarding our last major finding, patients with chronic heart failure had lower values in muscle oxygen saturation of the vastus lateralis muscle at rest and higher values at maximum load as well as lower isometric peak torque values compared to healthy controls (Fig.
4). Our results concerning muscle oxygen saturation of the vastus lateralis muscle at rest were 45.5 ± 3.9% and 52.4 ± 4.5% (− 13.2%) for patients and healthy controls, respectively. Another study also found lower values in patients with chronic heart failure at rest, but these were not statistically significant (67.9 ± 4.0% vs. 70.0 ± 5.4%; − 3.0%) [
19]. However, in our study, the muscle oxygen saturation of the biceps brachii muscle at rest showed lower values for patients as well (59.2 ± 11.7% vs. 76.7 ± 6.3%; − 22.3%). The muscle oxygen saturation of vastus lateralis muscle at maximum load was higher in patients (35.5 ± 8.8% vs. 24.2 ± 3.7%; + 46.7%), meaning healthy controls may use their oxygen reserves more efficiently compared to patients. The lower muscle oxygen saturation at rest and lower exploitation of oxygen reserves during load of the patients may be caused by the reduced peripheral perfusion, the adaptive mitochondrial dysfunction as well as the shift in muscle-fibre types, whereby slow, oxidative type I fibres are being replaced by fast, glycolytic type IIb fibres [
8,
14,
47]. Our results concerning isometric peak torque were 111 ± 21 Nm and 173 ± 44 Nm (− 35.8%) for patients and healthy controls, respectively, and are supported by previous studies, which investigated both groups separately (up to − 35.3%) [
23,
24]. The difference between both groups can be explained by the abovementioned peripheral changes, possibly resulting in the lower muscle mass of the patients with chronic heart failure [
8,
23]. As mentioned above regarding central factors, peripheral factors also show high intra- and interindividual variabilities (Fig.
3) [
15]. Overall, the results show that patients with chronic heart failure have peripheral differences compared to healthy controls, which should be considered in diagnosis and subsequently in therapy. The observed intra- and interindividual variabilities in patients with chronic heart failure could also help to implement therapy on a more individual basis.
Taken together, central and peripheral factors may affect the maximum oxygen uptake in patients with chronic heart failure. Thus, it is promising to measure both types of factors in clinical settings to allow more effective and individually adjusted therapies. The cardiac power output should be gaining increasing importance in diagnosis, follow-ups, and prognosis of heart failure, because of its possible superior prognostic impact compared to maximum oxygen uptake [
9‐
11]. Additionally, peripheral factors should be addressed simultaneously to clarify if a low maximum oxygen uptake is primarily based on central or peripheral factors. This can also be helpful for transplantation decisions in the future [
6] for which however more research is needed.
While our study increased the knowledge concerning non-invasively measured central and peripheral factors of oxygen uptake in patients with chronic heart failure, some limitations should be acknowledged. Firstly, we investigated a relatively small sample size, which caused large confidence intervals and unclear differences between the groups. A larger sample size would allow a better generalization. Additionally, a crucial point of our statistical approach is the definition of the smallest worthwhile difference. Compared to sport science, the definition is less approved in sport medical settings [
44]. Moreover, the exact etiology of the heart failure of our patients remain unknown and limit more mechanistic pathophysiological discussions [
15,
16]. The reason to exclude the etiology was that the potential trigger for the chronic heart failure of our patients was stretching far back into the past. Lastly, it is known that the reliability of the device used for the near-infrared spectroscopy decreases with increasing load [
40] and that differences in skinfold thickness between both groups were evident. Thus, differences in maximum load [
40] and skinfold thickness [
48] between both groups may have had an impact on our near infrared spectroscopy outcomes. Further studies are needed to address these points.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.