The effect of aerobic interval training and continuous training on exercise capacity and its determinants.

Objective We aimed to investigate (1) the effects of aerobic interval training (AIT) and aerobic continuous training (ACT) on (sub)maximal exercise measures and its determinants including endothelial function, muscle strength and cardiac autonomic function, and (2) the relationship between exercise capacity and these determinants. Methods Two-hundred coronary artery disease (CAD) patients (58.4 ± 9.1 years) were randomized to AIT or ACT for 12 weeks. All patients performed a cardiopulmonary exercise test and endothelial function measurements before and after the intervention; a subpopulation underwent muscle strength and heart rate variability (HRV) assessments. Results The VO2, heart rate and workload at peak and at first and second ventilatory threshold increased (P-time <0.001); the oxygen uptake efficiency slope (P-time <0.001) and half time of peak VO2 (P-time <0.001) improved. Endothelial function and heart rate recovery (HRR) at 1 and 2 min improved (P-time <0.001), while measures of muscle strength and HRV did not change. Both interventions were equally effective. Significant correlations were found between baseline peak VO2 and (1) quadriceps strength (r = 0.44; P < 0.001); (2) HRR at 2 min (r = 0.46; P < 0.001). Changes in peak VO2 correlated significantly with changes in (1) FMD (ρ = 0.17; P < 0.05); (2) quadriceps strength (r = 0.23; P < 0.05); (3) HRR at 2 min (ρ = 0.18; P < 0.05) and Total power of HRV (ρ = 0.41; P < 0.05). Conclusions This multicentre trial shows equal improvements in maximal and submaximal exercise capacity, endothelial function and HRR after AIT and ACT, while these training methods seem to be insufficient to improve muscle strength and HRV. Changes in peak VO2 were linked to changes in all underlying parameters.

Unraveling new mechanisms of exercise intolerance in chronic heart failure: role of exercise training.

Despite remarkable progress in the therapeutic approach of patients with chronic heart failure (CHF), exercise intolerance remains one of the hallmarks of the disease. During the past two decades, evidence has accumulated to underscore the key role of both endothelial dysfunction and skeletal muscle wasting in the process that gradually leads to physical incapacity. Whereas reverse ventricular remodeling has been attributed to aerobic exercise training, the vast majority of studies conducted in this specific patient population emphasize the reversal of peripheral abnormalities. In this review, we provide a general overview on underlying pathophysiological mechanisms. In addition, emphasis is put on recently identified pathways, which contribute to a deeper understanding of the main causes of exercise tolerance and the potential for reversal through exercise training. Recently, deficient bone marrow-related endothelial repair mechanisms have received considerable attention. Both acute exercise bouts, as well as exercise training, affect the mobilization of endothelial progenitor cells and their function. The observed changes following exercise training are believed to significantly contribute to improvement of peripheral endothelial function, as well as exercise capacity. With regard to skeletal muscle dysfunction and energy deprivation, adiponectin has been suggested to play a significant role. The demonstration of local skeletal muscle adiponectin resistance may provide an interesting and new link between the insulin resistant state and skeletal muscle wasting in CHF patients.

Effect of Training on Vascular Function and Repair in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Exercise training improves peak oxygen uptake (V.O2peak) in heart failure with preserved ejection fraction (HFpEF). Multiple adaptations have been addressed, but the role of circulating endothelium-repairing cells and vascular function have not been well defined. OBJECTIVES: The authors investigated effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on vascular function and repair in HFpEF. METHODS: This study is a subanalysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure) study randomizing patients with HFpEF (n = 180) to HIIT, MICT, or guideline control. At baseline, 3, and 12 months, the authors measured peripheral arterial tonometry (valid baseline measurement in n = 109), flow-mediated dilation (n = 59), augmentation index (n = 94), and flow cytometry (n = 136) for endothelial progenitor cells and angiogenic T cells. Abnormal values were defined as outside 90% of published sex-specific reference values. RESULTS: At baseline, abnormal values (%) were observed for augmentation index in 66%, peripheral arterial tonometry in 17%, flow-mediated dilation in 25%, endothelial progenitor cells in 42%, and angiogenic T cells in 18%. These parameters did not change significantly after 3 or 12 months of HIIT or MICT. Results remained unchanged when confining analysis to patients with high adherence to training. CONCLUSIONS: In patients with HFpEF, high augmentation index was common, but endothelial function and levels of endothelium-repairing cells were normal in most patients. Aerobic exercise training did not change vascular function or cellular endothelial repair. Improved vascular function did not significantly contribute to the V.O2peak improvement after different training intensities in HFpEF, contrary to previous studies in heart failure with reduced ejection fraction and coronary artery disease. (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure [OptimEx-Clin]; NCT02078947).

Exercise acutely reverses dysfunction of circulating angiogenic cells in chronic heart failure.

AIMS: Recruitment of endothelial progenitor cells (EPCs) and enhanced activity of circulating angiogenic cells (CACs) might explain the benefits of exercise training in reversing endothelial dysfunction in chronic heart failure (CHF) patients. We studied baseline EPC numbers and CAC function and the effect of a single exercise bout. METHODS AND RESULTS: Forty-one CHF patients (mild, n = 22; severe, n = 19) and 13 healthy subjects were included. Migratory activity of CACs was evaluated in vitro and circulating CD34+ and CD34+/KDR+ (EPC) cells were quantified by flow cytometry before and after cardiopulmonary exercise testing (CPET). Circulating stromal cell-derived factor-1alpha (SDF-1alpha) and vascular endothelial growth factor (VEGF) concentrations were measured. Both CAC migration as well as CD34+ cell numbers were significantly reduced in CHF, whereas CD34+/KDR+ cells were not different from controls. Endothelial dysfunction was related to impaired CAC migration (r = 0.318, P = 0.023). Cardiopulmonary exercise testing improved CAC migration in severe (+52%, P < 0.005) and mild CHF (+31%, P < 0.005), restoring it to levels similar to controls. Following CPET, SDF-1alpha increased in healthy controls and mild CHF (P < 0.005). Vascular endothelial growth factor, CD34+, and CD34+/KDR+ cell numbers remained unchanged. CONCLUSION: The present findings reveal a potent stimulus of acute exercise to reverse CAC dysfunction in CHF patients with endothelial dysfunction.

Plasma-Derived microRNAs Are Influenced by Acute and Chronic Exercise in Patients With Heart Failure With Reduced Ejection Fraction.

Background: Exercise training improves VO2peak in heart failure with reduced ejection fraction (HFrEF), but the effect is highly variable as it is dependent on peripheral adaptations. We evaluated changes in plasma-derived miRNAs by acute and chronic exercise to investigate whether these can mechanistically be involved in the variability of exercise-induced adaptations. Methods: Twenty-five male HFrEF patients (left ventricular ejection fraction < 40%, New York Heart Association class ≥ II) participated in a 15-week combined strength and aerobic training program. The effect of training on plasma miRNA levels was compared to 21 male age-matched sedentary HFrEF controls. Additionally, the effect of a single acute exercise bout on plasma miRNA levels was assessed. Levels of 5 miRNAs involved in pathways relevant for exercise adaptation (miR-23a, miR-140, miR-146a, miR-191, and miR-210) were quantified using RT-qPCR and correlated with cardiopulmonary exercise test (CPET), echocardiographic, vascular function, and muscle strength variables. Results: Expression levels of miR-146a decreased with training compared to controls. Acute exercise resulted in a decrease in miR-191 before, but not after training. Baseline miR-23a predicted change in VO2peak independent of age and left ventricular ejection fraction (LVEF). Baseline miR-140 was independently correlated with change in load at the respiratory compensation point and change in body mass index, and baseline miR-146a with change in left ventricular mass index. Conclusion: Plasma-derived miRNAs may reflect the underlying mechanisms of exercise-induced adaptation. In HFrEF patients, baseline miR-23a predicted VO2peak response to training. Several miRNAs were influenced by acute or repeated exercise. These findings warrant exploration in larger patient populations and further mechanistic in vitro studies on their molecular involvement.

Circulating microRNA as predictors for exercise response in heart failure with reduced ejection fraction.

AIMS: Exercise training is a powerful adjunctive therapy in patients with heart failure with reduced ejection fraction (HFrEF), but ca. 55% of patients fail to improve VO2peak. We hypothesize that circulating microRNAs (miRNAs), as epigenetic determinants of VO2peak, can distinguish exercise responders (ER) from exercise non-responders (ENR). METHODS AND RESULTS: We analysed 377 miRNAs in 18 male HFrEF patients (9 ER and 9 ENR) prior to 15 weeks of exercise training using a miRNA array. ER and ENR were defined as change in VO2peak of >20% or <6%, respectively. First, unsupervised clustering analysis of the miRNA pattern was performed. Second, differential expression of miRNA in ER and ENR was analysed and related to percent change in VO2peak. Third, a gene set enrichment analysis was conducted to detect targeted genes and pathways. Baseline characteristics and training volume were similar between ER and ENR. Unsupervised clustering analysis of miRNAs distinguished ER from ENR with 83% accuracy. A total of 57 miRNAs were differentially expressed in ENR vs. ER. A panel of seven miRNAs up-regulated in ENR (Let-7b, miR-23a, miR-140, miR-146a, miR-191, miR-210, and miR-339-5p) correlated with %changeVO2peak (all P < 0.05) and predicted ENR with area under the receiver operating characteristic curves ≥0.77. Multiple pathways involved in exercise adaptation processes were identified. CONCLUSION: A fingerprint of seven miRNAs involved in exercise adaptation processes is highly correlated with VO2peak trainability in HFrEF, which holds promise for the prediction of training response and patient-targeted exercise prescription.

Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With Preserved Ejection Fraction: A Subanalysis of the OptimEx-Clin Study.

AIMS: Iron deficiency (ID) is linked to reduced aerobic exercise capacity and poor prognosis in patients with heart failure (HF) with reduced ejection fraction (HFrEF); however, data for HF with preserved ejection fraction (HFpEF) is scarce. We assessed the relationship between iron status and diastolic dysfunction as well as aerobic exercise capacity in HFpEF, and the contribution of iron status to patient phenotyping. METHODS AND RESULTS: Among 180 patients with HFpEF (66% women; median age, 71 years) recruited for the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx-Clin) trial, baseline iron status, including iron, ferritin, and transferrin saturation, was analyzed (n = 169) in addition to exercise capacity (peak oxygen uptake [peak V̇O2]) and diastolic function (E/e'). ID was present in 60% of patients and was more common in women. In multivariable linear regression models, we found that diastolic function and peak V̇O2 were independently related to iron parameters; however, these relationships were present only in patients with HFpEF and ID [E/e' and iron: ß-0.19 (95% confidence interval -0.32, -0.07), p = 0.003; E/e' and transferrin saturation: ß-0.16 (-0.28, -0.04), p = 0.011; peak V̇O2 and iron: ß 3.76 (1.08, 6.44), p = 0.007; peak V̇O2 and transferrin saturation: ß 3.58 (0.99, 6.16), p = 0.007]. Applying machine learning, patients were classified into three phenogroups. One phenogroup was predominantly characterized by the female sex and few HFpEF risk factors but a high prevalence of ID (86%, p < 0.001 vs. other phenogroups). When excluding ID from the phenotyping analysis, results were negatively influenced. CONCLUSION: Iron parameters are independently associated with impaired diastolic function and low aerobic capacity in patients with HFpEF and ID. Patient phenotyping in HFpEF is influenced by including ID. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02078947.

miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial.

AIMS: In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients. METHODS AND RESULTS: We selected HFpEF patients from the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx) study which attended ≥70% of training sessions during 3 months (n = 51). Patients were defined as HR with a change in peakV·O2 above median (6.4%), and LR as below median (n = 30 and n = 21, respectively). Clinical, ergospirometric, and echocardiographic characteristics were similar between LR and HR. We performed an miRNA array (n = 377 miRNAs) in 14 age- and sex-matched patients. A total of 10 miRNAs were upregulated in LR, of which 4 correlated with peakV·O2. Validation in the remaining 37 patients indicated that high miR-181c predicted reduced peakV·O2 response (multiple linear regression, ß = -2.60, P = 0.011), and LR status (multiple logistic regression, odds ratio = 0.48, P = 0.010), independent of age, sex, body mass index, and resting heart rate. Furthermore, miR-181c decreased in LR after exercise training (P-group = 0.030, P-time = 0.048, P-interaction = 0.037). An in silico pathway analysis identified several downstream targets involved in exercise adaptation. CONCLUSIONS: Circulating miR-181c is a marker of the response to exercise training in HFpEF patients. High miR-181c levels can aid in identifying LR prior to training, providing the possibility for individualized management.

Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure.

Alterations in circulating angiogenic cells (CAC) and endothelial progenitor cells (EPC), known to contribute to endothelial repair, could explain the reversal of endothelial function in response to exercise training. Moreover, training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout. We studied the impact of exercise training on CAC function and numbers of CD34(+)/KDR(+) EPC in patients with chronic heart failure (CHF) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients. Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group (n = 17) and 10 healthy age-matched subjects. At baseline and follow-up, flow-mediated dilation was assessed and graded exercise testing (GXT) was performed. Before and immediately after GXT, CAC migratory capacity was assessed in vitro and circulating CD34(+)/KDR(+) EPC were quantified using flow cytometry. At baseline, CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT. Training corrected endothelial dysfunction, which coincided with a 77% increase in CAC migration (P = 0.0001). Moreover, the GXT-induced improvement detected at baseline was no longer observed after training. Numbers of CD34(+)/KDR(+) EPC increased following 6-month exercise training (P = 0.021), but were not affected by GXT, either prior or post-training. In conclusion, the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34(+)/KDR(+) EPC, which is accompanied by improvement of peripheral endothelial function. The acute exercise-induced changes in CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to functional endothelial repair.

Maintaining physical fitness of patients with chronic heart failure: a randomized controlled trial.

BACKGROUND: We aimed to compare the effects of three different training advices, after 1 year, following a 6 months supervised cardiac rehabilitation period in patients with chronic heart failure (CHF). METHODS: Sixty-nine CHF patients were randomized, at the end of their rehabilitation period, either to usual care (UC) or to UC and controlled home training (HT), prolonged supervised training (ST) or preferred training (PT). Treadmill cardio-pulmonary exercise testing was performed before rehabilitation, postrehabilitation and thereafter at 3-month intervals during the 1-year follow-up. submaximal exercise capacity [Oxygen consumption and workload at the respiratory compensation point (VO2RCP, WattRCP) and submaximal workload (SMW) efficiency (SMW/HR) at 70% of the initial maximal workload] was chosen as a primary endpoint, because health status in CHF patients depends largely on their ability to perform activities at a submaximal level. RESULTS: After 6 months of rehabilitation, the four groups (UC, HT, ST and PT) were comparable with regard to cardiac rehabilitation-derived benefit, both at the submaximal and maximal level. Although exercise capacity during follow-up declined in both UC and HT patients, ST and especially PT patients maintained and even improved VO2peak and VO2RCP. However, only PT patients managed to maintain or even increase submaximal (WattRCP and SMW/HR ratio) workload (P=0.045 and <0.0001 for interaction, respectively). Ventilatory-derived prognostic markers during treadmill cardio pulmonary exercise testing evolved similarly in the four subgroups. CONCLUSION: This study suggests that engagement in physical training of their own choice (PT), might be the optimal training modality for maintaining physical capacity in CHF patients.

Combined endurance-resistance training vs. endurance training in patients with chronic heart failure: a prospective randomized study.

AIMS: This study was designed to compare the effects of combined endurance-resistance training (CT) with endurance training (ET) only on submaximal and maximal exercise capacity, ventilatory prognostic parameters, safety issues, and quality of life in patients with chronic heart failure (CHF). METHODS AND RESULTS: Fifty-eight CHF patients (NYHA class II-III) were randomized either to 6 months CT [n = 28, 58 years, left ventricular ejection fraction (LVEF) 26%, VO(2)peak 18.1 mL/kg/min] or ET (n = 30, 59 years, LVEF 23%, VO(2)peak 21.3 mL/kg/min). The increase in steady-state workload (P = 0.007) and the decrease in heart rate at SSW (P = 0.002) were significantly larger in CT- compared with ET-trained patients. Maximal exercise capacity (i.e. VO(2)peak, maximal workload) and work-economy (Wattmax/VO(2)peak) evolved similarly. VO(2)peak halftime was reduced following CT (P = 0.001). Maximal strength in upper limbs increased significantly (P < 0.001) in favour of the CT group. CT also had a beneficial effect on health-related quality of life, i.e. 60% of CT-trained patients vs. 28% of ET-trained patients reported a decrease in cardiac symptoms (OR = 3.86, 95% CI 1.11-12.46, P = 0.03). There were no differences with regard to improved LVEF, evolution of left ventricular dimensions, nor outcome data (mortality and cardiovascular hospital admissions during follow-up). CONCLUSION: In CHF patients, CT had a more pronounced effect on submaximal exercise capacity, muscle strength, and quality of life. The absence of unfavourable effects on left ventricular remodelling and outcome parameters is reassuring and might facilitate further implementation of this particular training modality.

Predictors of response to exercise training in patients with coronary artery disease - a subanalysis of the SAINTEX-CAD study.

Exercise training improves peak oxygen uptake, an important predictor of mortality in coronary artery disease patients. The influence of clinical and disease characteristics on training response is not well established in coronary artery disease. Therefore, we aimed to evaluate whether baseline cardiovascular disease variables and training intensity can predict the maximal aerobic response to exercise training. The Study on Aerobic INTerval EXercise training in coronary artery disease patients (SAINTEX-CAD) previously showed that 12 weeks of aerobic interval training and continuous training equally improved peak oxygen uptake in coronary artery disease patients. We identified 24 exercise non-responders (change peak oxygen uptake <1 ml/kg/min) among 167 participants in SAINTEX-CAD. In a between-group comparison, exercise non-responders were older, their baseline peak oxygen uptake and oxygen uptake efficiency slope were higher, and exercise non-responders were more frequently included after elective percutaneous coronary intervention (all p < 0.05). In multiple logistic regression analysis, age (odds ratio = 1.11 (1.04-1.18), p = 0.001), history of elective percutaneous coronary intervention (odds ratio = 3.31 (1.12-9.76), p = 0.030) and higher baseline peak oxygen uptake (odds ratio = 1.16 (1.06-1.27), p = 0.001) were independent predictors of exercise non-response. In multiple linear regression analysis, age (ß = -0.605, p = 0.001), history of elective percutaneous coronary intervention (ß = -15.401, p = 0.010), training intensity (ß=0.447, p = 0.008), baseline physical activity (ß=0.014, p = 0.003) and oxygen uptake efficiency slope (ß = -0.014, p < 0.001) predicted percentage change in peak oxygen uptake and explained 41% of the variability in percentage change in peak oxygen uptake. To summarize, 14% of coronary artery disease patients were exercise non-responders. Higher baseline peak oxygen uptake and oxygen uptake efficiency slope, history of elective percutaneous coronary intervention, older age, lower training intensity and lower baseline physical activity were predictors of training non-response. Identification of patients with a large likelihood of non-response is a first step towards patient tailored exercise programmes.

Impact of aerobic interval training and continuous training on left ventricular geometry and function: a SAINTEX-CAD substudy.

BACKGROUND: Increase of exercise capacity (peak VO2) after cardiac rehabilitation improves outcome in patients with coronary artery disease (CAD). Systolic and diastolic function have been associated with peak VO2, but their role towards improvement of exercise capacity remains unclear. It is unknown which exercise intensity has the most beneficial impact on left ventricular (LV) geometry and function in CAD patients without heart failure. METHODS: 200 stable CAD patients without heart failure were randomized to 3months of aerobic interval training (AIT) or aerobic continuous training (ACT). Cardiopulmonary exercise test and transthoracic echocardiography were scheduled before and after 3months of training. RESULTS: At baseline, a higher peak VO2 correlated with lower LV posterior wall thickness (p=0.002), higher LV ejection fraction (p=0.008), better LV global longitudinal strain (p=0.043) and lower E/e' (0=0.001). After multivariate stepwise regression analysis only E/é remained an independent predictor of peak VO2 (p=0.042). Improvement of peak VO2 after 3months of training correlated with reverse remodeling of the interventricular septum (p=0.005), enlargement of LV diastolic volume (p=0.007) and increase of LV stroke volume (p=0.018) but not with other indices of systolic or diastolic function. Significant reduction of the interventricular septum thickness after cardiac rehabilitation was observed (p=0.012), with a trend towards more reverse remodeling after ACT compared to AIT (p=0.054). In contrast, there were no changes in other parameters of LV geometry, diastolic or systolic function. CONCLUSION: Systolic and diastolic function are determinants of baseline exercise capacity in CAD patients without heart failure, but do not seem to mediate improvement of peak VO2 after either AIT or ACT.

The long-term effects of a randomized trial comparing aerobic interval versus continuous training in coronary artery disease patients: 1-year data from the SAINTEX-CAD study.

BACKGROUND: Aerobic interval training (AIT) and aerobic continuous training (ACT) both improve physical fitness (peak VO2) in coronary artery disease patients. However, little is known about the long-term effects of AIT and ACT on peak VO2 and exercise adherence. DESIGN: This study is a randomized clinical multicenter trial. METHODS: In total, 163 patients were assessed after 12 weeks of AIT or ACT and 12 months after their enrollment. Physical fitness and physical activity measures served as the primary outcomes, and peripheral endothelial function, cardiovascular risk factors and quality of life (QoL) served as the secondary outcomes. RESULTS: Twenty-six patients dropped out during the intervention; 11 were lost during the follow-up period. Dropouts (n = 37) consisted of more women (p = 0.001) compared to completers (n = 163). Physical fitness (VO2, heart rate and workload at peak and at thresholds) and physical activity (steps, active energy expenditure [kcal], physical activity duration [minutes]) were preserved at the 1-year follow-up (p-time > 0.05) after both AIT and ACT (p-interaction > 0.05). Forty percent of patients showed increased peak VO2, 52% showed increased active energy expenditure and 91.2% met the recommended levels of 150 minutes/week of moderate physical activity (p-group > 0.05). Further, peripheral endothelial function, QoL and cardiovascular risk factors, except systolic blood pressure (p-time < 0.05), remained stable (p-time > 0.05) after both AIT and ACT (p-interaction > 0.05). CONCLUSION: The short-term improvements of center-based AIT and ACT on physical fitness, physical activity, peripheral endothelial function, cardiovascular risk factors and QoL are sustained after a 1-year follow-up period. The majority of patients (>90%) met the recommended physical activity levels of 150 minutes/week.

Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease: the SAINTEX-CAD study.

BACKGROUND: Exercise-based cardiac rehabilitation increases peak oxygen uptake (peak VO2), which is an important predictor of mortality in cardiac patients. However, it remains unclear which exercise characteristics are most effective for improving peak VO2 in coronary artery disease (CAD) patients. Proof of concept papers comparing Aerobic Interval Training (AIT) and Moderate Continuous Training (MCT) were conducted in small sample sizes and findings were inconsistent and heterogeneous. Therefore, we aimed to compare the effects of AIT and Aerobic Continuous Training (ACT) on peak VO2, peripheral endothelial function, cardiovascular risk factors, quality of life and safety, in a large multicentre study. METHODS: Two-hundred CAD patients (LVEF >40%, 90% men, mean age 58.4 ± 9.1 years) were randomized to a supervised 12-week cardiac rehabilitation programme of three weekly sessions of either AIT (90-95% of peak heart rate (HR)) or ACT (70-75% of peak HR) on a bicycle. Primary outcome was peak VO2; secondary outcomes were peripheral endothelial function, cardiovascular risk factors, quality of life and safety. RESULTS: Peak VO2 (ml/kg/min) increased significantly in both groups (AIT 22.7 ± 17.6% versus ACT 20.3 ± 15.3%; p-time<0.001). In addition, flow-mediated dilation (AIT+34.1% (range -69.8 to 646%) versus ACT+7.14% (range -66.7 to 503%); p-time<0.001) quality of life and some other cardiovascular risk factors including resting diastolic blood pressure and HDL-C improved significantly after training. Improvements were equal for both training interventions. CONCLUSIONS: Contrary to earlier smaller trials, we observed similar improvements in exercise capacity and peripheral endothelial function following AIT and ACT in a large population of CAD patients.

Rationale and design of a randomized trial on the effectiveness of aerobic interval training in patients with coronary artery disease: the SAINTEX-CAD study.

BACKGROUND: Exercise-based cardiac rehabilitation is considered an important adjunct treatment and secondary prevention measure in patients with coronary artery disease (CAD). However, the issues of training modality and exercise intensity for CAD patients remain controversial. OBJECTIVE: Main aim of the present study is to test the hypothesis that aerobic interval training (AIT) yields a larger gain in peak aerobic capacity (peakVO2) compared to a similar training programme of moderate continuous training (MCT) in CAD patients. STUDY DESIGN: In this multicentre study stable CAD patients with left ventricular ejection fraction>40% will be randomized after recent myocardial infarction or revascularization (PCI or CABG) to a supervised 12-week programme of three weekly sessions of either AIT (85-90% of peak oxygen uptake [peakVO2], 90-95% of peak heart rate) or MCT (60-70% of peakVO2, 65-75% of peak heart rate). The primary endpoint of the study is the change of peakVO2 after 12 weeks training. Secondary endpoints include safety, changes in peripheral endothelial vascular function, the evolution of traditional cardiovascular risk factors, quality of life and the number and function of circulating endothelial progenitor cells as well as endothelial microparticles. Possible differences in terms of long-term adherence to prescribed exercise regimens will be assessed by regular physical activity questionnaires, accelerometry and reassessment of peakVO2 12 months after randomization. A total number of 200 patients will be randomized in a 1:1 manner (significance level of 0.05 and statistical power of 0.90). Enrolment started December 2010; last enrolment is expected for February 2013.

Impact of exercise testing mode on exercise parameters in patients with chronic heart failure.

AIM: To verify the impact of testing mode on maximal, sub-maximal parameters and on cardiopulmonary exercise test (CPET) derived prognostic markers in patients with chronic heart failure (CHF). METHOD: 55 patients (age 60.3 years ±11.1) with CHF (ejection fraction 26 %±8) underwent a maximal CPET on a bicycle and on a treadmill, in a random order, within one week. Maximal, sub-maximal parameters and CPET derived prognostic markers were compared. RESULTS: VO(2)peak and VO(2)peak corrected for lean body mass were significantly higher on treadmill compared to bicycle (+11%, p < 0.0001). This was also the case for the following sub-maximal parameters; heart rate, workload and VO(2) at ventilatory anaerobic threshold and VO(2) at the respiratory compensation point (RCP). In contrast, both VE/VCO(2) slopes (start to RCP and start to end test) were similar. Time to 1/2 VO(2)peak was longer and circulatory power was higher on the treadmill compared to exercise testing on the bicycle. CONCLUSION: The results of the present study suggest that the mode of exercise testing significantly affects absolute values for VO(2)peak but does not greatly impact the prognostic utility of the VE/VCO(2) slope in patients with moderate to severe CHF. Besides the consequences of these findings in terms of prognostication, testing mode should be taken into consideration when exercise prescription is based on VO(2)peak.

Comparison of three methods to identify the anaerobic threshold during maximal exercise testing in patients with chronic heart failure.

OBJECTIVE: Exercise training efficiently improves peak oxygen uptake (V˙O2peak) in patients with chronic heart failure. To optimize training-derived benefit, higher exercise intensities are being explored. The correct identification of anaerobic threshold is important to allow safe and effective exercise prescription. DESIGN: During 48 cardiopulmonary exercise tests obtained in patients with chronic heart failure (59.6 ± 11 yrs; left ventricular ejection fraction, 27.9% ± 9%), ventilatory gas analysis findings and lactate measurements were collected. Three technicians independently determined the respiratory compensation point (RCP), the heart rate turning point (HRTP) and the second lactate turning point (LTP2). Thereafter, exercise intensity (target heart rate and workload) was calculated and compared between the three methods applied. RESULTS: Patients had significantly reduced maximal exercise capacity (68% ± 21% of predicted V˙O2peak) and chronotropic incompetence (74% ± 7% of predicted peak heart rate). Heart rate, workload, and V˙O2 at HRTP and at RCP were not different, but at LTP2, these parameters were significantly (P < 0.0001) higher. Mean target heart rate and target workload calculated using the LTP2 were 5% and 12% higher compared with those calculated using HRTP and RCP, respectively. The calculation of target heart rate based on LTP2 was 5% and 10% higher in 12 of 48 (25%) and 6 of 48 (12.5%) patients, respectively, compared with the other two methods. CONCLUSIONS: In patients with chronic heart failure, RCP and HRTP, determined during cardiopulmonary exercise tests, precede the occurrence of LTP2. Target heart rates and workloads used to prescribe tailored exercise training in patients with chronic heart failure based on LTP2 are significantly higher than those derived from HRTP and RCP.