Printer Friendly

Aerobic Training Intensity for Improved Endothelial Function in Heart Failure Patients: A Systematic Review and Meta-Analysis.

1. Introduction

Results of numerous studies and meta-analyses have now shown that exercise training is not only safe but is associated with a range of physiological, functional, and clinical benefits in patients with heart failure (HF) [1-3]. While exercise interventions in HF patients have utilised a range of training modalities, aerobic or endurance training is the most investigated and has been shown to improve a range of parameters in HF patients [1, 4], including endothelial function [5]. Endothelial dysfunction is associated with the pathogenesis and progression of HF [6] and flow-mediated dilation (FMD), a noninvasive assessment of endothelial function, has been shown to be predictive of deterioration and death [7] in HF patients. Aerobic exercise training improves endothelial dependent vasodilation primarily by improving nitic oxide (NO) bioavailability [8].

Despite a large number of exercise training studies it was not until 2011 that a consensus document by the Heart Failure Association (HFA) and European Association for Cardiovascular Prevention and Rehabilitation (EACPR) provided a detailed and comprehensive guideline for exercise training in HF patients [9]. However, while aerobic exercise is now a feature of cardiac rehabilitation guidelines around the world, training program characteristics still vary considerably and the focus of current and emerging research is on identifying the exercise modality, dose, and intensity that will deliver optimal benefits [10-13]. While all training characteristics will likely influence results to some degree, the role of exercise intensity in cardiac rehabilitation is considered a key issue [14]. As the pattern of blood flow and amount of shear stress [8] that occur during exercise may be related to the specific training characteristics, including training intensity, ascertaining an optimal training protocol is important.

A meta-analysis in HF patients by Ismail and colleagues (2013) [12] demonstrated that as exercise intensity increases the magnitude of change in V[O.sub.2peak] also increases. In addition, a considerable body of evidence is mounting in relation to aerobic intermittent or interval training in clinical populations including HF patients [15, 16], and more specifically in relation to high-intensity interval training (HIIT) [15] for improving a range of physiological, functional and clinical parameters, including vascular function [5].

While exercise intensity is associated with the magnitude of change in V[O.sub.2peak] in HF patients [12], the relationship between aerobic intensity and endothelial function is not clear. In healthy men, high-intensity exercise has been shown to increase oxidative stress reducing the bioavailability of NO and possibly negating the positive effect of exercise induced shear stress on endothelial function [17]. However, increases in antioxidant levels and greater improvements in FMD from HIIT compared to moderate intensity continuous training (MICT) in heart failure patients [5] suggest that intensity may have a role in the endothelial response to exercise in this population.

In a range of clinical populations both moderate [18] and high-intensity [19,20] aerobic training have significantly improved FMD. A recent meta-analysis [21] across a diverse population reported a significant improvement in FMD from aerobic exercise and a significant dose-response relationship between intensity and FMD. In addition, Ramos and colleagues (2015) [22] examined the effects of high-intensity training, specifically HIIT compared to MICT across a diverse population, demonstrating HIIT to be more effective for improving FMD [22].

A number of aerobic exercise training studies have now investigated FMD in HF patients and therefore the primary aim of our paper was to conduct a systematic review and meta-analysis to investigate if training intensity reflects the magnitude of change in FMD.

2. Methods

2.1. Search Strategy. Potential studies were identified by conducting systematic searches of PubMed, Embase, CINAHL, SPORTDiscus, and the Cochrane Library of Controlled Trials up until 30 June 30, 2016. Searches included a mix of MeSH and free text terms related to the key concepts of heart failure, exercise training, endothelial function, and flow-mediated dilation. Additionally, systematic reviews, meta-analyses, and reference lists of papers were hand searched for additional studies. One reviewer (MJP) conducted the search; and full articles were assessed for eligibility by two reviewers (MJP and NAS). Two authors were contacted to provide additional information; one author did not respond and the second responded but was unable to provide any further details.

2.2. Study Selection. Randomised controlled trials and controlled trials of aerobic exercise training in heart failure patients with reduced ejection fractions (HFrEF) were included. Studies included in the review compare an aerobic training intervention to a no exercise or usual care control group or compared continuous aerobic training with interval or intermittent aerobic training. Only studies that measured endothelial function by flow-mediated dilation (FMD) measured via ultrasound reported as relative FMD% or absolute FMD (mm or [micro]m) in either the brachial or radial artery were included.

2.3. Data Extraction and Outcome Measures. Data were extracted by one reviewer (MJP). The primary outcome measure was flow-mediated dilation (FMD% or FMD absolute (mm)). Where FMD was reported as FMD% and FMD (mm), FMD% was utilised in the analysis.

2.4. Data Synthesis. Statistical analyses were performed using Revman 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark). The individual meta-analyses were completed for continuous data by using the change in the mean and standard deviation (SD). The primary outcome measure was FMD%. Where the change in mean and SD were not reported, the change in mean was calculated by subtracting the preintervention mean form the postintervention mean, and Revman 5.3 enabled calculations of SD using number of participants in each group, within or between group p values or 95% CI. In cases where exact p values were not provided, we used default values; for example, p < 0.05 becomes p = 0.049, p < 0.01 becomes p = 0.0099, and p = not significant becomes p = 0.051. Data not provided in main text or tables were extracted from figures. A random effects inverse variance was used with the effects measure of standardised mean difference (SMD). We utilised the widely accepted guideline for SMD interpretation [23], with 0.2 defined as small, 0.5 medium, and 0.8 as large. Where a study included multiple intervention groups and a control group, the sample size of the control group was divided by the number of intervention groups to eliminate over inflation of the sample size. We used a 5% level of significance and a 95% CI to report change in outcome measures. Aerobic intensity was defined and classified according to the ACSM (2011) [24]. Where prescribed intensity overlapped between two intensity classifications an additional analysis was conducted by reallocation of the studies to the alternative classification.

2.5. Heterogeneity and Publication Bias. Heterogeneity was quantified using the [I.sup.2] test [25]. Values range from 0% (homogeneity) to 100% (highly heterogeneity) [25]. Egger tests and funnel plots [26] were provided to assess risk of publication bias.

2.6. Study Quality. Study quality was assessed by using the TESTEX, the tool for assessment of study quality and reporting, designed specifically for use in exercise training studies [27]. This is a 15-point scale that assesses study quality (maximum 5 points) and reporting (maximum 10 points). Two reviewers (MJP and NAS) conducted quality assessment.

3. Results

The initial search identified 485 manuscripts. After removal of duplicates and exclusion of articles based on abstract and title, 26 full-text articles remained for screening. Full screening resulted in 13 articles meeting the stated inclusion criteria (Figure 1 PRISMA statement). The aerobic exercise intervention characteristics of the 13 studies in the metaanalysis are included in Table 1. Details of full-text articles reviewed but excluded are provided in Supplementary Table S1 in Supplementary Material available online at https://doi.org/10.1155/2017/2450202. Full participant details are provided in Supplementary Table S2.

3.1. Study Characteristics. Thirteen [5, 28-39] studies provided a total of 458 participants diagnosed with HFrEF, 264 exercising participants, and 194 nonexercising control subjects. Twelve studies [5, 28-37, 39] included a usual care control group, of these, two studies [5, 28] included two different aerobic intervention groups. One study [38] did not include a control group and only compared intervention groups undertaking different aerobic exercise protocols. Ten studies [5, 29-33, 35-38] randomised participants, two studies were nonrandomised controlled trials [34, 39], and one study randomised participants between two exercise interventions but the control group was nonrandomised [28]. The average age of participants ranged between 49 [+ or -] 5yrs and 76 [+ or -] 13yrs and sex distribution was predominantly male. Brachial baseline FMD% ranged from ~3% to >7% and reported that baseline radial FMD% ranged from ~6% to >12% (Supplementary Table S2).

3.2. Intervention Details. Intervention duration ranged from 4 weeks to 6 months, the frequency of sessions ranged from 2 days per week to daily, and the duration of exercise sessions ranged from 10 to 60 minutes. All studies performed an exercise test from which training intensity was prescribed and cycling was the most common mode of aerobic exercise. For pooled analysis, aerobic training intensity was classified according to ACSM (2011) [24]. The training protocol of four studies [5, 28, 34, 38] utilised interval/intermittent training and of these, three [5, 28, 34] utilised a training intensity deemed as high-intensity interval training (HIIT). Two [28, 38] studies employed short to moderate length intervals [40] and two [5, 34] utilised long length [40] intervals classified as a 4x4 HIIT protocol, but with different intensities. Seven [5, 28, 31, 34, 35, 37, 38] studies reported on how intensity was monitored, but only four [5, 28, 31, 34] studies reported actual or perceived (RPE) training intensity of participants and only one [32] reported actual energy expenditure (Supplementary Table S3). Seven [5, 28, 30-32, 34, 37] studies reported session attendance percentages and 11 studies [5,28-35, 37, 38] reported on the occurrence of any adverse events (Supplementary Table S4). The assessment of FMD varied between studies (Supplementary Table S5) and 10 studies [5, 28-31, 33-35, 38, 39] assessed FMD in the Brachial Artery (BA), with the Radial Artery utilised in three studies [32, 36, 37].

4. Outcome Measures

4.1. Flow-Mediated Dilation (FMD)

4.1.1. Moderate Aerobic Intensity versus Control. Pooled data from seven studies [5, 28-32, 35] that utilised moderate intensity demonstrated a significant improvement in FMD, exercise versus control, SMD of 1.00 (95% CI 0.19 to 1.80, p = 0.02) (Figure 2(a)). The significance level increased with removal of the one non-RCT [28], SMD of 1.24 (95% CI 0.42 to 2.06, p = 0.003). One [35] study prescribed an intensity range that incorporates both the moderate and vigorous intensity definition, and removal of the study resulted in an increased SMD of 1.22 (95% CI 0.36 to 2.07, p = 0.005) (Figure 2(b)), which increased further with removal of the one non-RCT [28] [SMD of 1.53 (95% CI 0.72 to 2.35, p = 0.0002)].

4.1.2. Vigorous Aerobic Intensity versus Control. Pooled data from seven studies [5,28, 33, 34, 36, 37, 39] utilising vigorous intensity demonstrated a significant improvement in FMD, SMD of 1.21 (95% CI 0.60 to 1.82, p = 0.0001) (Figure 3(a)). Removal of the three non-RCTs [28, 34, 39] increased the significance, SMD of 1.69 (95% CI 0.97 to 2.40, p < 0.00001). Reclassification of the one [35] study that straddled both moderate and vigorous intensity decreased SMD to 1.05 (95% CI 0.43 to 1.68, p = 0.001) (Figure 3(b)); however with removal of the three non-RCTs [28, 34, 39] SMD increased to 1.43 (95% CI 0.56 to 2.30, p = 0.001).

4.1.3. AerobicInterval/Intermittent versus Continuous. Pooled data from three studies [5, 28, 38] demonstrated a nonsignificant change in FMD with interval training versus control; SMD of 0.56 (95% CI -0.49 to 1.61, p = 0.30) (Supplementary Figure S1). With removal of the one non-RCT [28] the change in FMD increased but remained nonsignificant [SMD of 1.00 (95% CI -0.33 to 2.33, p = 0.14)]. One [38] study utilised a moderate intensity, with the remaining two studies [5, 28] utilising a high intensity. With removal of the one [38] moderate intensity study the result remained nonsignificant for HIIT versus continuous [SMD of 0.70 (95% CI -1.27 to 2.69, p = 0.49)].

4.1.4. HIIT versus Control. Pooled data from three studies [5, 28, 34] that included a HIIT and control group, indicated a trend toward improvement with HIIT in FMD; however this was not significant, SMD of 1.80 (95% CI -0.69 to 4.29, p = 0.16) (Supplementary Figure S2). Two [28, 34] of the three studies were however non-RCTs.

4.2. Endothelial-Independent Dilation. Six [28-30, 33, 34, 36] of the included studies noted the assessment of endothelial-independent vasodilation. Five studies [28-30, 33, 34] provided relative% change in arterial diameter, while one study [36] provided both absolute and relative% change. The endothelial-independent response did not differ significantly between exercise and control, SMD of -0.02 (95% CI -0.85 to 0.82, p = 0.97) (Supplementary Figure S3).

4.3. Study Quality Assessment. The median TESTEX score was 9 (Supplementary Table S6). While RCTs noted participant randomisation, specific details were lacking from the majority of studies. The majority of studies lost points in the areas of allocation concealment and activity monitoring in the control group.

4.4. Heterogeneity and Publication Bias. All analyses demonstrated moderate to high heterogeneity. Funnel plots demonstrated some evidence of publication bias.

5. Discussion

This work analysed the effects of aerobic training intensity on FMD in patients with chronic heart failure. Our primary finding shows that aerobic exercise training significantly improves endothelial function, assessed via FMD, in patients with heart failure. Our pooled data failed to find a significant change in endothelial-independent vasodilation, indicating that the improvement occurred at the level of the endothelium [41]. All but two [28, 35] of the studies included in our analysis found improvements in brachial or radial artery FMD. Interestingly, while Kobayashi et al. (2003) [35] failed to find any improvement in upper limb FMD they did report a significant improvement in lower limb artery FMD (posterior tibial artery).

Training intensity is considered a key component in determining optimal outcomes in cardiac rehabilitation [14] and our analysis demonstrated that both moderate and vigorous intensity, defined according to ACSM (2011) [24], significantly improved FMD of the brachial or radial artery. However, whether or not the magnitude of improvement increased with intensity remains unclear. As only four studies reported actual training intensities, our analysis of intensity was based on the prescribed training intensity for the exercise intervention. Whether or not vigorous or moderate intensity provided greater improvements in FMD was dependent upon the allocation of one [35] study, which prescribed a training intensity range that fell within both moderate and vigorous categories. Two analyses were therefore conducted to ascertain the effect of this study, and due to the nonsignificant finding of the study, reallocation demonstrated contrasting results. Based on the analysis we therefore cannot conclude that the magnitude of the improvement in FMD increases with intensity as was recently reported in the case of V[O.sub.2peak] by Ismail and colleagues [12]. Additionally, it is likely that the result would also vary depending on the actual definition or range of a particular intensity adopted, which varies between organization [24, 42], and whether or not the actual training intensities were as prescribed.

Since the impressive findings of Wisloff et al. (2007) [5] there has been an increased interest in aerobic intermittent/interval training and some guidelines [9] now advocate for this as a form of aerobic training in stable HF patients, although the actual prescribed intensity of the intervals still vary. We therefore conducted an analysis of HIIT compared to MICT. Our analysis of FMD indicated a trend toward interval or HIIT providing a greater improvement than MICT; however, the pooled results were not significant. Only the study of Wisloff et al. [5] demonstrated HIIT as significantly superior to MICT. However, only two [5, 38] of the three studies included in our analysis were RCTs and while the RCT of Smart and Steele (2012) [38] utilised interval training, the intensity of the intervals did not fall within the definition of HIIT [40]. Interval or intermittent training can be performed at any intensity; however, HIIT has been shown to invoke more significant improvements in V[O.sub.2peak] compared to MICT in HF patients [15,16].

The broad definition of HIIT also means that a range of protocols are employed in both research and practice and a large number of variables can be manipulated in prescribing HIIT [43]. All three studies in our analysis of HIIT versus MICT utilised different protocols, with only Wisloff et al. (2007) [5] employing a long interval (4 x 4) protocol, which may account for some of the contrasting results between studies. Different interval/HIIT protocols may have different physiological responses and may impact the amount of shear stress [5, 22, 28]. For this reason a long HIIT protocol may be more effective [22]. Interestingly the participants in the Wisloff et al. [5] study also had lower baseline FMD% (<4%) than participants in the other two studies [28, 38] and therefore could provide a further explanation of the contrasting results, as lower baseline FMD% is one factor suggested as differentiating FMD responders from nonresponders [44]. Our nonsignificant finding is in contrast to the significant and superior improvement in FMD after HIIT compared to MICT in studies across a diverse population [22], although in CAD patients the recent SAINTEX-CAD study [45] reported significant improvements in FMD from HIIT and MICT with no difference between groups. Recently it was demonstrated in obese adults that HIIT and MICT may result in different vascular adaptations with HIIT improving FMD and MICT improving resting brachial diameter [46]. However, no studies in our review reported a significant change in resting arterial diameter after MICT. Interestingly, a recent meta-analysis that compared HIIT to MICT to investigate other clinical parameters in heart failure patients (not FMD) revealed mixed findings [13], while data from previous meta-analyses have shown HIIT more effective than MICT in improving V[O.sub.2peak]

In our pooled analysis of HIIT compared to no training, despite a trend toward HIIT, we failed to find a significant change in FMD. However, two of the three studies were non-RCTs [28, 34]. Of the three included studies, the non-RCT of Isaksen et al. (2015) [34] and RCT of Wisloff et al. (2007) [5] both reported a significant change in FMD in training groups after intervention with no change in controls, and interestingly both studies utilised a 4x4 HIIT protocol, which maybe a more optimal protocol to improve vascular function [22]. Interestingly, a short duration HIIT interval (30 seconds work; 60 seconds rest) utilised by Anagnostakou et al. [47] in a comparison of HIIT to combined HIIT and resistance training failed to elicit a significant improvement in FMD in a HIIT only training group. However, FMD improved in a combined HIIT and resistance training group. Of particular interest is that, in the Isaksen et al. [34] study, while HR data was not stored for intensity analysis on any variables, they do note that, in a separate analysis on V[O.sub.2peak], the improvement in V[O.sub.2peak] was almost doubled in patients who reported an average RPE [greater than or equal to] 16, and while no details are provided on FMD, one can question whether this may have occurred with FMD, indicating the role of intensity.

As there are still unanswered questions in relation to the role of endothelial dysfunction in the development and symptoms of HF patients with preserved ejection fractions [48] our analysis only included patients with reduced ejection fractions. Therefore our analysis cannot be generalised to HFpEF patients. Additionally, only minimal studies to date exist that have utilised aerobic training and investigated FMD. Kitzman and colleagues (2013) [49] failed to find any significant change in FMD following 16 weeks of high-intensity aerobic training (70% V[O.sub.2max]), while more recently Angadi et al. (2015) [50] in a relatively small, short duration (4 weeks) study compared HIIT and MICT and failed to find a significant change in FMD in either group.

Strengths and Limitations in the Systematic Review and MetaAnalysis. To the best of our knowledge this is the first metaanalysis that provides analysis on aerobic training intensity and endothelial function in heart failure patients. The major limitation of the review is the high level of heterogeneity among studies. Differences in the methodological assessment of FMD and medication use may have contributed to the level of heterogeneity. Another limitation of the review is the classification of exercise intensity. We classified aerobic intensity according to the ACSM (2011) guidelines [24], which provides intensity ranges based on % HRR or V[O.sub.2] reserve (V[O.sub.2]R), V[O.sub.2max], H[R.sub.max], RPE, or Metabolic Equivalent of Task (METS). Over the years these ranges have changed which would change the classification of studies. Additionally, intensity ranges definedby other organizations [42] differ from the ACSM [24]. As the majority of studies did not report on the actual training intensities of the sessions, whether or not the mean training intensity was firstly within the prescribed intensity range for the duration of the intervention and secondly whether the mean training intensity was closer to the upper or lower end of the prescribed ranges could not be ascertained. We were unable to conduct an analysis according to different intensity domains and thresholds, as opposed to ranges, as suggested by Mezzani et al. (2012) [14], as the relevant information could not be extracted from all studies. In regard to data pooling, we measured the difference between preintervention and postintervention means; however, in cases where exact p values, within groups or between groups, or 95% CI were not available, default values for p were utilised and this may introduce errors. Additionally, data from some studies was extracted from figures; this in itself has the potential to introduce errors.

6. Conclusion

This meta-analysis found that both vigorous and moderate aerobic exercise training improves endothelial function, assessed by FMD, in heart failure patients with reduced ejection fractions. Future studies investigating FMD responses to different training intensities including high-intensity training protocols will further assist in providing more evidence as to optimal aerobic training intensity prescription to elicit superior improvements in endothelial function as well as other physiological and clinically relevant endpoints.

https://doi.org/10.1155/2017/2450202

Disclosure

This work received no financial support and has no relationship to industry. The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Competing Interests

The authors report no relationships that could be construed as a conflict of interests.

References

[1] M. J. Haykowsky, Y. Liang, D. Pechter, L. W. Jones, F. A. McAlister, and A. M. Clark, "A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed," Journal of the American College of Cardiology, vol. 49, no. 24, pp. 2329-2336, 2007.

[2] N. A. Smart, T. Meyer, J. A. Butterfield et al., "Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure," European Journal of Preventive Cardiology, vol. 19, no. 3, pp. 428-435, 2012.

[3] G. Dieberg, H. Ismail, F. Giallauria, and N. A. Smart, "Clinical outcomes and cardiovascular responses to exercise training in heart failure patients with preserved ejection fraction: a systematic review and meta-analysis," Journal of Applied Physiology, vol. 119, no. 6, pp. 726-733, 2015.

[4] G. Cipriano Jr., V T. F. Cipriano, V. Z. Maldaner Da Silva et al., "Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis," Heart Failure Reviews, vol. 19, no. 5, pp. 655-667, 2014.

[5] U. Wisloff, A. Stoylen, J. P. Loennechen et al., "Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study," Circulation, vol. 115, no. 24, pp. 3086-3094, 2007.

[6] C. N. Marti, M. Gheorghiade, A. P. Kalogeropoulos, V. V. Georgiopoulou, A. A. Quyyumi, and J. Butler, "Endothelial dysfunction, arterial stiffness, and heart failure," Journal of the American College of Cardiology, vol. 60, no. 16, pp. 1455-1469, 2012.

[7] B. Meyer, D. Mortl, K. Strecker et al., "Flow-mediated vasodilation predicts outcome in patients with chronic heart failure: comparison with B-type natriuretic peptide," Journal of the American College of Cardiology, vol. 46, no. 6, pp. 1011-1018, 2005.

[8] D. J. Green, "Exercise training as vascular medicine: direct impacts on the vasculature in humans," Exercise and Sport Sciences Reviews, vol. 37, no. 4, pp. 196-202, 2009.

[9] M. F. Piepoli, V. Conraads, U. CorrA et al., "Exercise training in heart failure: From theory to practice. A consensus document of the heart failure association and the european association for cardiovascular prevention and rehabilitation," European Journal of Heart Failure, vol. 13, no. 4, pp. 347-357, 2011.

[10] T. Vromen, J. J. Kraal, J. Kuiper, R. F. Spee, N. Peek, and H. M. Kemps, "The influence of training characteristics on the effect of aerobic exercise training in patients with chronic heart failure: a meta-regression analysis," International Journal of Cardiology, vol. 208, pp. 120-127, 2016.

[11] H. Ismail, J. R. McFarlane, G. Dieberg, and N. A. Smart, "Exercise training program characteristics and magnitude of change in functional capacity of heart failure patients," International Journal of Cardiology, vol. 171, no. 1, pp. 62-65, 2014.

[12] H. Ismail, J. R. McFarlane, A. H. Nojoumian, G. Dieberg, and N. A. Smart, "Clinical Outcomes and cardiovascular responses to different exercise training intensities in patients with heart failure. A systematic review and meta-analysis," JACC: Heart Failure, vol. 1, no. 6, pp. 514-522, 2013.

[13] J. Cornelis, P. Beckers, J. Taeymans, C. Vrints, and D. Vissers, "Comparing exercise training modalities in heart failure: a systematic review and meta-analysis," International Journal of Cardiology, vol. 221, pp. 867-876, 2016.

[14] A. Mezzani, L. F. Hamm, A. M. Jones et al., "Aerobic exercise intensity assessment and prescription in cardiac rehabilitation: a joint position statement of the European Association for Cardiovascular Prevention and Rehabilitation, the American Association of Cardiovascular and Pulmonary Rehabilitation and the Canadian Association of Cardiac Rehabilitation," European Journal of Preventive Cardiology, vol. 20, no. 3, pp. 442-467, 2013.

[15] M. J. Haykowsky, M. P. Timmons, C. Kruger, M. McNeely, D. A. Taylor, and A. M. Clark, "Meta-analysis of aerobic interval training on exercise capacity and systolic function in patients with heart failure and reduced ejection fractions," The American Journal of Cardiology, vol. 111, no. 10, pp. 1466-1469, 2013.

[16] N. A. Smart, G. Dieberg, and F. Giallauria, "Intermittent versus continuous exercise training in chronic heart failure: a metaanalysis," International Journal of Cardiology, vol. 166, no. 2, pp. 352-358, 2013.

[17] C. Goto, Y. Higashi, M. Kimura et al., "Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress," Circulation, vol. 108, no. 5, pp. 530-535, 2003.

[18] M. Vona, G. M. Codeluppi, T. Iannino, E. Ferrari, J. Bogousslavsky, and L. K. Von Segesser, "Effects of different types of exercise training followed by detraining on endothelium-dependent dilation in patients with recent myocardial infarction," Circulation, vol. 119, no. 12, pp. 1601-1608, 2009.

[19] T. S. Hermann, C. H. Dall, S. B. Christensen, J. P. Goetze, E. Prescott, and F. Gustafsson, "Effect of high intensity exercise on peak oxygen uptake and endothelial function in long-term heart transplant recipients," American Journal of Transplantation, vol. 11, no. 3, pp. 536-541, 2011.

[20] P. S. Munk, E. M. Staal, N. Butt, K. Isaksen, and A. I. Larsen, "High-intensity interval training may reduce in-stent restenosis following percutaneous coronary intervention with stent implantation: a randomized controlled trial evaluating the relationship to endothelial function and inflammation," American Heart Journal, vol. 158, no. 5, pp. 734-741, 2009.

[21] A. W. Ashor, J. Lara, M. Siervo et al., "Exercise modalities and endothelial function: a systematic review and dose-response meta-analysis of randomized controlled trials," Sports Medicine, vol. 45, no. 2, pp. 279-296, 2015.

[22] J. S. Ramos, L. C. Dalleck, A. E. Tjonna, K. S. Beetham, and J. S. Coombes, "The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis," Sports Medicine, vol. 45, no. 5, pp. 679-692, 2015.

[23] J. Cohen, Statistical Power Analysis for the Behavioral Sciences, Lawrence Erlbaum Associates, Hillside, NJ, USA, 1988.

[24] C. E. Garber, B. Blissmer, M. R. Deschenes et al., "Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise," Medicine and Science in Sports and Exercise, vol. 43, no. 7, pp. 1334-1359, 2011.

[25] J. P. T. Higgins, S. G. Thompson, J. J. Deeks, and D. G. Altman, "Measuring inconsistency in meta-analyses," British Medical Journal, vol. 327, no. 7414, pp. 557-560, 2003.

[26] M. Egger, G. D. Smith, M. Schneider, and C. Minder, "Bias in meta-analysis detected by a simple, graphical test," British Medical Journal, vol. 315, no. 7109, pp. 629-634, 1997

[27] N. A. Smart, M. Waldron, H. Ismail et al., "Validation of a new tool for the assessment of study quality and reporting in exercise training studies: TESTEX," International Journal of Evidence-Based Healthcare, vol. 13, no. 1, pp. 9-18, 2015.

[28] N. M. M. Benda, J. P. H. Seeger, G. G. C. F. Stevens et al., "Effects of high-intensity interval training versus continuous training on physical fitness, cardiovascular function and quality of life in heart failure patients," PLoS ONE, vol. 10, no. 10, Article ID e0141256, 2015.

[29] R. Belardinelli, F. Capestro, A. Misiani, P. Scipione, and D. Georgiou, "Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy," European Journal of Cardiovascular Prevention and Rehabilitation, vol. 13, no. 5, pp. 818-825, 2006.

[30] R. Belardinelli, F. Lacalaprice, E. Faccenda, A. Purcaro, and G. Perna, "Effects of short-term moderate exercise training on sexual function in male patients with chronic stable heart failure," International Journal of Cardiology, vol. 101, no. 1, pp. 83-90, 2005.

[31] E. Eleuteri, A. Mezzani, A. Di Stefano et al., "Aerobic training and angiogenesis activation in patients with stable chronic heart failure: a preliminary report," Biomarkers, vol. 18, no. 5, pp. 418-424, 2013.

[32] S. Erbs, R. Hollriegel, A. Linke et al., "Exercise training in patients with advanced chronic heart failure (NYHA IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function," Circulation: Heart Failure, vol. 3, no. 4, pp. 486-494, 2010.

[33] M. Guazzi, G. Reina, G. Tumminello, and M. D. Guazzi, "Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure," Journal of Applied Physiology, vol. 97, no. 5, pp. 1866-1873, 2004.

[34] K. Isaksen, P. S. Munk, T. Valborgland, and A. I. Larsen, "Aerobic interval training in patients with heart failure and an implantable cardioverter defibrillator: a controlled study evaluating feasibility and effect," European Journal of Preventive Cardiology, vol. 22, no. 3, pp. 296-303, 2015.

[35] N. Kobayashi, Y. Tsuruya, T. Iwasawa et al., "Exercise training in patients with chronic heart failure improves endothelial function predominantly in the trained extremities," Circulation Journal, vol. 67, no. 6, pp. 505-510, 2003.

[36] A. Linke, N. Schoene, S. Gielen et al., "Endothelial dysfunction in patients with chronic heart failure: systemic effects of lowerlimb exercise training," Journal of the American College of Cardiology, vol. 37, no. 2, pp. 392-397, 2001.

[37] M. Sandri, M. Viehmann, V. Adams et al., "Chronic heart failure and aging--effects of exercise training on endothelial function and mechanisms of endothelial regeneration: results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study," European Journal of Preventive Cardiology, vol. 23, no. 4, pp. 349-358, 2016.

[38] N. A. Smart and M. Steele, "A Comparison of 16 weeks of continuous vs intermittent exercise training in chronic heart failure patients," Congestive Heart Failure, vol. 18, no. 4, pp. 205-211, 2012.

[39] E. M. Van Craenenbroeck, V Y. Hoymans, P. J. Beckers et al., "Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure," Basic Research in Cardiology, vol. 105, no. 5, pp. 665-676, 2010.

[40] T. Guiraud, A. Nigam, V. Gremeaux, P. Meyer, M. Juneau, and L. Bosquet, "High-intensity interval training in cardiac rehabilitation," Sports Medicine, vol. 42, no. 7, pp. 587-605, 2012.

[41] A. Barac, U. Campia, and J. A. Panza, "Methods for evaluating endothelial function in humans," Hypertension, vol. 49, no. 4, pp. 748-760, 2007.

[42] K. Norton, L. Norton, and D. Sadgrove, "Position statement on physical activity and exercise intensity terminology," Journal of Science and Medicine in Sport, vol. 13, no. 5, pp. 496-502, 2010.

[43] M. Buchheit and P. B. Laursen, "High-intensity interval training, solutions to the programming puzzle: part I: cardiopulmonary emphasis," Sports Medicine, vol. 43, no. 5, pp. 313-338, 2013.

[44] D. J. Green, T. Eijsvogels, Y. M. Bouts et al., "Exercise training and artery function in humans: nonresponse and its relationship to cardiovascular risk factors," Journal of Applied Physiology, vol. 117, no. 4, pp. 345-352, 2014.

[45] V. M. Conraads, N. Pattyn, C. De Maeyer et al., "Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease: The SAINTEX-CAD Study," International Journal of Cardiology, vol. 179, pp. 203-210, 2015.

[46] B. J. Sawyer, W. J. Tucker, D. M. Bhammar, J. R. Ryder, K. L. Sweazea, and G. A. Gaesser, "Effects of high-intensity interval training and moderate-intensity continuous training on endothelial function and cardiometabolic risk markers in obese adults," Journal of Applied Physiology, vol. 121, no. 1, pp. 279-288, 2016.

[47] V. Anagnostakou, K. Chatzimichail, S. Dimopoulos et al., "Effects of interval cycle training with or without strength training on vascular reactivity in heart failure patients," Journal of Cardiac Failure, vol. 17, no. 7, pp. 585-591, 2011.

[48] D. W. Kitzman and M. J. Haykowsky, "Vascular dysfunction in heart failure with preserved ejection fraction," Journal of Cardiac Failure, vol. 22, no. 1, pp. 12-16, 2016.

[49] D. W. Kitzman, P H. Brubaker, D. M. Herrington et al., "Effect of endurance exercise training on endothelial function and arterial stiffness in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial," Journal of the American College of Cardiology, vol. 62, no. 7, pp. 584-592, 2013.

[50] S. S. Angadi, F. Mookadam, C. D. Lee, W. J. Tucker, M. J. Haykowsky, and G. A. Gaesser, "High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study," Journal of Applied Physiology, vol. 119, no. 6, pp. 753-758, 2015.

M. J. Pearson and N. A. Smart

School of Science and Technology, University of New England, Armidale, NSW 2351, Australia

Correspondence should be addressed to N. A. Smart; nsmart2@une.edu.au

Received 9 December 2016; Accepted 7 February 2017; Published 27 February 2017

Academic Editor: Stephan von Haehling

Caption: Figure 1: PRISMA flow diagram.
Table 1: Aerobic exercise characteristics of studies included in
meta-analysis.

Study             Study      Sample size    Intervention     Training
                  design     (completed/      duration       modality
                              analysed)        (weeks)

Benda et al.       Non-          29              12           Cycle
(2015) [28]       RCT(1)

Belardinelli et     RCT          52               8           Cycle
al. (2006) [29]

Belardinelli et     RCT          59               8           Cycle
al. (2005) [30]

Eleuteri et al.
(2013) [31]         RCT          21              12           Cycle

Erbs et al.         RCT          34              12           Cycle
(2010) [32]                                                  1 x GS *

Guazzi et al.
(2004) [33]         RCT          31               8           Cycle

Isaksen et al.
(2015) [34]       Non-RCT        35              12          Cycle or
                                                            treadmill

Kobayashi et        RCT          28              12           Cycle
al. (2003) [35]

Linke et al.        RCT          22               4           Cycle
(2001) [36]

Sandriet al.        RCT          60               4
(2015) [37]                                                   Cycle

                                                             1 x GS *

Smart and           RCT          23              16           Cycle
Steele (2012)
[38]

Van               Non-RCT        38              26         Ambulatory
Craenenbroeck                                                  base
et al. (2010)
[39]

Wisloffet al.       RCT          26              12         Treadmill/
(2007) [5]                                                     home
                                                             walking

Study              Frequency           Session duration
                   (per wk.)

Benda et al.           2                 35 min (HUT)
(2015) [28]                              30 min (CT)
                                    plus 10 min warm-up,
                                  5 min cooldown each group

Belardinelli et        3                    40 min
al. (2006) [29]                      plus 15 min warm-up
                                   stretch, 5 min cooldown

Belardinelli et        3                    40 min
al. (2005) [30]                      plus 15 min warm-up
                                   stretch, 5 min cooldown

Eleuteri et al.                             30 min
(2013) [31]            5          plus 5 min warm-up, 5 min
                                           cooldown

Erbs et al.          Daily                20-30 min
(2010) [32]        +1 GS wk.       (plus 1 x 60 min GS/wk.)

Guazzi et al.                               30 min
(2004) [33]            4          plus 5 min warm-up, 5 min
                                           cooldown

Isaksen et al.                              25 min
(2015) [34]            3          plus 15 min warm-up, 5 min
                                       cooldown, 15 min
                                       strength/stretch

Kobayashi et          2-3           2 x 15 min session/day
al. (2003) [35]     (2x day)          (30 min/day total)

Linke et al.         daily                  10 min
(2001) [36]       (6x per day)       1 (60 min/day total)

Sandriet al.                        15-20 min (-60 min/day
(2015) [37]            5                    total)
                    (4x per         plus 5 min warm-up and
                    weekday)      cooldown (plus 1 x 60 min
                                         GS per/wk.)

Smart and              3                 60 min (INT)
Steele (2012)                           30 min (CONT)
[38]

Van                    3                    60 min
Craenenbroeck
et al. (2010)
[39]

Wisloffet al.                      28 min (AIT) plus 10 min
(2007) [5]             3                   warm-up
                                        47 min (MICT)

Study                Prescribed exercise intensity

Benda et al.          HUT: 10 x 1 min @ 90% max.
(2015) [28]        workload (RPE15-17) separated by
                      2.5 min @ 30% max. workload
                    CT: @60-75% max. workload (RPE
                                12-14)
                     warm-up @ 40% max. Workload &
                     cooldown @ 30% max. workload

Belardinelli et           60% V[O.sub.2peak]
al. (2006) [29]

Belardinelli et           60% V[O.sub.2peak]
al. (2005) [30]

Eleuteri et al.    HR & power @ VAT (cycle @ 60RPM)
(2013) [31]         (VAT ~ 60% V[O.sub.2max]) (1)

Erbs et al.              HR @60% V[O.sub.2max]
(2010) [32]

Guazzi et al.     60% HRR wk. 1-2, [up arrow] 80% HRR
(2004) [33]                     @ wk. 3

Isaksen et al.     4x4 HUT @ 85% H[R.sub.max] (~RPE
(2015) [34]       15-17) separated by 3 min recovery
                   @ 60-70% H[R.sub.max], warm-up @
                          60-70% H[R.sub.max]

Kobayashi et       HR @ VAT (-60-70% V[O.sub.2max])
al. (2003) [35]

Linke et al.              70% V[O.sub.2peak]
(2001) [36]

Sandriet al.            70% of symptom limited
(2015) [37]                  V[O.sub.2max]

Smart and           INT: work: rest (60 s: 60 s) @
Steele (2012)      60-70% V[O.sub.2peak] CT: 60-70%
[38]                V[O.sub.2peak] (cycle @ 60 RPM)

Van                90% HR @ respiratory compensation
Craenenbroeck                    point
et al. (2010)
[39]

Wisloffet al.           AIT: 4 min x 4 @ 90-95%
(2007) [5]        H[R.sub.max], separated by 3 min @
                   50-70% H[R.sub.max], MICT: @ 70-
                         75% H[R.sub.max]

AIT: aerobic interval training, Con: control, CT: continuous
training, GS: group session, HUT: high intensity interval training,
HR: heart rate, H[R.sub.max]: maximum heart rate, H[R.sub,peak]:
peak heart rate, HRR: heart rate reserve, MIACT: moderate intensity
aerobic training, MICT: moderate continuous training, non/RCT:
nonrandomised controlled trial, RCT: randomised controlled trial,
RPE: rating of perceived exertion, RPM: revolutions per minute, VAT:
ventilatory anaerobic threshold, V[O.sub.2peak]: peak oxygen uptake,
and V[O.sub.2max]: maximal oxygen uptake. (1) Two exercise groups
randomised, but control group not randomised. (1) V[O.sub.2] @ VT/
V[O.sub.2peak] = 8.8/14.8 = 59.5% of V[O.sub.2peak]. * 1 group
session per week composed of walking, calisthenics, and ball games.

Figure 2: (a) FMD: moderate aerobic training versus control. (b)
FMD: moderate aerobic training versus control (removal of Kobayashi
study from moderate intensity).

Study or                  Exercise                    Control
subgroup
                  Mean      SD     Total     Mean       SD      Total

Belardinelli et   2.75    3.3431    30     -0.0172    1.1825     29
al., 2005

Belardinelli et   2.35    3.5137    30      -0.05     0.1133     22
al., 2006

Benda et al.      -0.4    0.5622    10       0.1      0.8545      4
(MCT), 2015

Eleuteri et        1.9    2.4932    11       0.5      1.4064     10
al., 2013

Erbs et al.,      7.43     2.28     17       0.09      2.18      17
2010

Kobayashi et      0.22    0.383     14       0.32      0.557     14
al., 2003

Wisleff et al.    4.61     2.06      8       -0.3     0.1901      4
(MCT), 2007

Total (95% CI)                      120                          100

Heterogeneity: [[tau].sub.2] = 0.94; [chi square] = 38.37, df = 6
(p A64< 0.00001); [I.sub.2] = 84%

Test for overall effect: Z = 2.42 (p = 0.02)

(a)

Study or                  Moderate                    Control
subgroup

                  Mean      SD     Total     Mean       SD      Total

Belardinelli et   2.75    3.3431    30     -0.0172    1.1825     29
al., 2005

Belardinelli et   2.35    3.5137    30      -0.05     0.1133     22
al., 2006

Benda et al.      -0.4    0.5622    10       0.1      0.8545      4
(MCT), 2015

Eleuteri et        1.9    2.4932    11       0.5      1.40646    10
al., 2013

Erbs et al.,      7.43     2.28     17       0.09      2.18      17
2010

Wisleff et al.    4.61     2.06      8       -0.3     0.1901      4
(MCT), 2007

Total (95% CI)                      106                          86

Heterogeneity: [[tau].sub.2] = 0.87; [chi square] = 28.67, df = 5
(p < 0.0001); [I.sub.2] = 83%

Test for overall effect: Z = 2.80 (p = 0.005)

Study or                    Std. mean difference
subgroup          Weight     IV, random, 95% CI

Belardinelli et    16.6%     1.08 [0.53, 1.63]
al., 2005

Belardinelli et    16.5%     0.88 [0.31, 1.46]
al., 2006

Benda et al.       12.9%    -0.72 [-1.92, 0.48]
(MCT), 2015

Eleuteri et        14.8%     0.66 [-0.23, 1.54]
al., 2013

Erbs et al.,       13.8%      3.21 [2.16,4.27]
2010

Kobayashi et       15.6%    -0.20 [-0.95, 0.54]
al., 2003

Wisleff et al.     9.7%       2.62 [0.87,4.38]
(MCT), 2007

Total (95% CI)    100.0%     1.00 [0.19, 1.80]

Heterogeneity: [[tau].sub.2] = 0.94; [chi square] = 38.37, df = 6
(p A64< 0.00001); [I.sub.2] = 84%

Test for overall effect: Z = 2.42 (p = 0.02)

(a)

Study or          Weight    Std. mean difference
subgroup

                             IV, random, 95% CI

Belardinelli et    19.9%     1.08 [0.53, 1.63]
al., 2005

Belardinelli et    19.7%      0.88 [0.31,1.46]
al., 2006

Benda et al.       15.2%    -0.72 [-1.92, 0.48]
(MCT), 2015

Eleuteri et        17.6%     0.66 [-0.23, 1.54]
al., 2013

Erbs et al.,       16.3%      3.21 [2.16,4.27]
2010

Wisleff et al.     11.3%      2.62 [0.87,4.38]
(MCT), 2007

Total (95% CI)    100.0%      1.22 [0.36,2.07]

Heterogeneity: [[tau].sub.2] = 0.87; [chi square] = 28.67, df = 5
(p < 0.0001); [I.sub.2] = 83%

Test for overall effect: Z = 2.80 (p = 0.005)

Figure 3: (a) FMD: vigorous aerobic training versus control. (b)
FMD: vigorous aerobic training versus control (reallocation of
Kobayashi from moderate to vigorous intensity).

Study or subgroup           Vigorous                  Control

                    Mean      SD      Total   Mean      SD      Total

Benda et al.        -0.6    0.8433     10      0.1    0.9759      5
(HIIT), 2015

Guazzi et al.,       3.4    4.6076     16     -0.51   0.9255     15
2004

Isaksen et al.,      3.5      4.2      24     -0.2      3.6      11
2015

Linke et al.,         6     4.3384     11      0.2    0.2993     11
2001

Sandri et al.        4.4    4.1158     15     -0.2     0.363     15
(+65 yrs), 2015

Sandri et al.        4.4    4.1158     15      0.3    0.5444     15
(-55 yrs), 2015

Van Craenenbroeck    1.4    2.0877     21     -0.7    2.1137     17
et al., 2010

Wisloff et al.      8.09     1.73       9     -0.3    0.2433      5
(AIT), 2007

Total (95% CI)                         121                       94

Heterogeneity: [[tau].sub.2] = 0.52; [chi square] = 24.87, df = 7
(p = 0.0008); [I.sub.2] = 72%

Test for overall effect: Z = 3.89 (p = 0.0001)

(a)

Study or subgroup           Vigorous                  Control

                    Mean      SD      Total   Mean      SD      Total

Benda et al.        -0.6    0.8433     10      0.1    0.9759      5
(HIIT), 2015

Guazzi et al.,       3.4    4.6076     16     -0.51   0.9255     15
2004

Isaksen et al.,      3.5      4.2      24     -0.2      3.6      11
2015

Kobayashi et al.,   0.22     0.383     14     0.32     0.557     14
2003

Linke et al.,         6     4.3384     11      0.2    0.2993     11
2001

Sandri et al.        4.4    4.1158     15     -0.2     0.363     15
(+65 yrs), 2015

Sandri et al.        4.4    4.1158     15      0.3    0.5444     15
(-55 yrs), 2015

Van Craenenbroeck    1.4    2.0877     21     -0.7    2.1137     17
et al., 2010

Wisloff et al.      8.09     1.73       9     -0.3    0.2433      5
(AIT), 2007

Total (95% CI)                         135                       108

Study or subgroup   Weight    Std. mean difference
                               IV, random, 95% CI

Benda et al.        11.5%     -0.74 [-1.86, 0.37]
(HIIT), 2015

Guazzi et al.,      14.4%      1.13 [0.36, 1.89]
2004

Isaksen et al.,     14.6%      0.90 [0.15, 1.65]
2015

Linke et al.,       12.2%       1.81 [0.79,2.84]
2001

Sandri et al.       13.9%      1.53 [0.70, 2.36]
(+65 yrs), 2015

Sandri et al.       14.1%      1.36 [0.55, 2.16]
(-55 yrs), 2015

Van Craenenbroeck   15.2%      0.98 [0.30, 1.66]
et al., 2010

Wisloff et al.       4.1%       5.53 [2.88,8.19]
(AIT), 2007

Total (95% CI)      100.0%     1.21 [0.60, 1.82]

Heterogeneity: [[tau].sub.2] = 0.52; [chi square] = 24.87, df = 7
(p = 0.0008); [I.sub.2] = 72%

Test for overall effect: Z = 3.89 (p = 0.0001)

(a)

Study or subgroup   Weight    Std. mean difference

                               IV, random, 95% CI

Benda et al.        10.3%      -0.74 [-1.86,0.37]
(HIIT), 2015

Guazzi et al.,      12.4%       1.13 [0.36,1.89]
2004

Isaksen et al.,     12.6%       0.90 [0.15,1.65]
2015

Kobayashi et al.,   12.6%      -0.20 [-0.95,0.54]
2003

Linke et al.,       10.8%       1.81 [0.79,2.84]
2001

Sandri et al.       12.1%      1.53 [0.70, 2.36]
(+65 yrs), 2015

Sandri et al.       12.2%       1.36 [0.55,2.16]
(-55 yrs), 2015

Van Craenenbroeck   13.0%      0.98 [0.30, 1.66]
et al., 2010

Wisloff et al.       4.1%       5.53 [2.88,8.19]
(AIT), 2007

Total (95% CI)      100.0%     1.05 [0.43, 1.68]

Heterogeneity: [[tau].sub.2] = 0.66; [chi square] = 35.38, df = 8
(p < 0.0001); [I.sub.2] = 77%
COPYRIGHT 2017 COPYRIGHT 2010 SAGE-Hindawi Access to Research
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Research Article
Author:Pearson, M.J.; Smart, N.A.
Publication:Cardiology Research and Practice
Date:Jan 1, 2017
Words:7800
Previous Article:The concordance between myocardial perfusion imaging and coronary angiography in detecting coronary artery disease: a retrospective study in a...
Next Article:Corrigendum to "Falls and Fractures in the Elderly with Sinus Node Disease: The Impact of Pacemaker Implantation".
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters