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.

Effects of aerobic interval training and continuous training on cellular markers of endothelial integrity in coronary artery disease: a SAINTEX-CAD substudy.

In this large multicenter trial, we aimed to assess the effect of aerobic exercise training in stable coronary artery disease (CAD) patients on cellular markers of endothelial integrity and to examine their relation with improvement of endothelial function. Two-hundred CAD patients (left ventricular ejection fraction > 40%, 90% male, mean age 58.4 ± 9.1 yr) were randomized on a 1:1 base to a supervised 12-wk rehabilitation program of either aerobic interval training or aerobic continuous training on a bicycle. At baseline and after 12 wk, numbers of circulating CD34(+)/KDR(+)/CD45dim endothelial progenitor cells (EPCs), CD31(+)/CD3(+)/CXCR4(+) angiogenic T cells, and CD31(+)/CD42b(-) endothelial microparticles (EMPs) were analyzed by flow cytometry. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery. After 12 wk of aerobic interval training or aerobic continuous training, numbers of circulating EPCs, angiogenic T cells, and EMPs were comparable with baseline levels. Whereas improvement in peak oxygen consumption was correlated to improvement in FMD (Pearson r = 0.17, P = 0.035), a direct correlation of baseline or posttraining EPCs, angiogenic T cells, and EMP levels with FMD was absent. Baseline EMPs related inversely to the magnitude of the increases in peak oxygen consumption (Spearman rho = -0.245, P = 0.027) and FMD (Spearman rho = -0.374, P = 0.001) following exercise training. In conclusion, endothelial function improvement in response to exercise training in patients with CAD did not relate to altered levels of EPCs and angiogenic T cells and/or a diminished shedding of EMPs into the circulation. EMP flow cytometry may be predictive of the increase in aerobic capacity and endothelial function.

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.

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.

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.

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.

Exercise training reduces circulating adiponectin levels in patients with chronic heart failure.

High adiponectin concentrations have emerged as an independent risk factor of outcome inpatients with CHF (chronic heart failure); however, modification of adiponectin in CHF patients has not been assessed to date. The aim of the present study was to investigate the effect of exercise training on adiponectin levels in CHF patients. A total of 80 patients with CHF due to systolic dysfunction were included. The effect of 4 months exercise training was studied in 46 patients,whereas the remaining 34 untrained CHF patients served as a sedentary control group. Circulating adiponectin concentrations, exercise capacity, anthropometric data and NT-proBNP (N-terminal pro-brain natriuretic peptide) levels were assessed. Adiponectin levels were significantly higher in CHF patients compared with healthy subjects [9.3 (7.1-16.1) and 4.9 (3.9-8.6) mg/l respectively;P=0.015]. Stratification of CHF patients according to tertiles of NT-proBNP revealed an increase in adiponectin with disease severity (P<0.0001). Exercise training reduced circulating adiponectin levels in CHF patients [10.7 (7.2-17.6) mg/l before training to 9.4 (5.9-14.8) mg/l after training;P=0.013], whereas no changes were observed in the sedentary CHF group [9.0 (7.0-13.5) mg/l before training and 10.1 (6.0-15.7) mg/l after a similar time interval]. A significant time x group interaction (P=0.008) was observed for the mean change in adiponectin between the trained and untrained CHF patients. Adiponectin concentrations were positively associated with NT-proBNP and HDL (high-density lipoprotein)-cholesterol and negatively correlated with BMI (body mass index), triacylglycerols and exercise capacity. In conclusion, circulating adiponectin concentrations are higher in CHF patients compared with healthy subjects and increase with disease severity.Exercise training for 4 months lowers circulating adiponectin levels.

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.

Circulating CD34+/KDR+ endothelial progenitor cells are reduced in chronic heart failure patients as a function of Type D personality.

The aim of the present study was to assess whether EPC (endothelial progenitor cell) number/function might be an explanatory factor for the observed relationship between Type D personality (a joint tendency towards negative affectivity and social inhibition) and poor cardiovascular prognosis. We also assessed whether the effect of a single exercise bout on EPC number/function was affected by Type D personality. A total of 35 sedentary men with CHF (chronic heart failure; left ventricular ejection fraction

Exercise capacity in chronic heart failure patients is related to active gene transcription in skeletal muscle and not apoptosis.

BACKGROUND: Muscle wasting partly explains exercise intolerance in chronic heart failure (CHF) patients. Skeletal muscle loss may result from apoptosis, and exercise training has been suggested to halt this process. The terminal deoxynucleotidyl transferase end-labeling (TUNEL) technique is frequently used to show apoptosis, but lacks specificity. METHODS AND RESULTS: Before and after 4 months exercise training, skeletal muscle biopsies of 16 CHF patients (59.4+/-2.2 years, 11 men, 50% ischemic etiology, ejection fraction 28.8+/-2.7%, 66.3+/-3.6% of predicted oxygen uptake) and eight sedentary controls were analyzed for apoptosis (TUNEL, including the stringent variant without proteinase K digestion, immunohistochemical analyses using antibodies against cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, PARP, and active gene transcription (anti-splicing factor SC-35). The number of TUNEL-positive nuclei in CHF patients was comparable with controls (3.2+/-0.7 vs. 3.1+/-1.7/mm(2), P=0.2) and was not related to exercise parameters. With the stringent TUNEL and both immunostaining techniques, apoptosis was not detected. Co-occurrence of TUNEL and of SC-35 splicing factor suggests that at least part of TUNEL-positive nuclei is undergoing active gene transcription and therefore is not apoptotic. The SC-35-positive area correlated with % of predicted oxygen uptake (r=0.6, P=0.02), Wattmax (r=0.7, P=0.005) and VE/VCO2 slope (r=-0.6, P=0.03). At baseline, SC-35 immunoreactive area was significantly larger than in controls (P=0.001), but after exercise training, the difference was minimized (P=0.07). CONCLUSION: Skeletal muscle apoptosis in CHF patients could not be confirmed. Active gene transcription might stain false positive for apoptotic nuclei with TUNEL. The level of active gene transcription/splicing was related to exercise performance.

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.

Exercise-induced biphasic increase in circulating NT-proBNP levels in patients with chronic heart failure.

BACKGROUND: Exercise increases natriuretic peptide levels in chronic heart failure (CHF) patients, but the effect is considered minor. We assessed acute and short-term release (<24 h) of NT-proBNP in CHF patients after a maximal cardiopulmonary exercise test (CPET) and 2 different submaximal training sessions. METHODS AND RESULTS: 102 CHF patients either performed CPET (Group 1), a 1 h endurance (Group 2) or a combined endurance-resistance training session (Group 3). NT-proBNP concentration was determined before, at exercise cessation and after 18-22 h (Protocol A). In 20 patients, samples were obtained before, at exercise cessation, after 15, 30, 45, 60, 90 min, 2, 3, 4, 5, 6, 12, 22 h (Protocol B). Protocol A: At peak exercise, a 15%, 11% and 17% relative increase (p<0.001 vs baseline, all 3 groups) was seen, with a return to baseline after 18-22 h. The increase correlated with indicators of more advanced heart failure. Protocol B: A biphasic pattern was derived with a first peak within 1 h of exercise termination and a second peak (39%, 31% and 33% higher than baseline; p<0.05, all 3 groups) after 4-12 h. CONCLUSIONS: The observed biphasic release of B-type natriuretic peptides supports standardization of sampling, taking recent exercise into account.

Predictive value of Type D personality for impaired endothelial function in patients with coronary artery disease.

BACKGROUND: Type D personality (high negative affectivity and social inhibition) is associated with cardiovascular events and coronary plaque severity. Whether Type D is also related to functional vasomotion abnormalities is unknown. We examined concurrent and predictive associations of Type D with endothelial dysfunction in patients with coronary artery disease (CAD). METHODS: At baseline, 180 CAD patients (90% men; M = 58.0 years) completed Type D (DS14) and depression scales, and entered a 12-week exercise program. Flow-mediated dilation (FMD) of the brachial artery and circulating CD34+/KDR+/CD45+dim endothelial progenitor cells (EPCs) were assessed at baseline, 3 months, and 12 months. Logistic regression and linear mixed models were used to analyze endothelial function. RESULTS: Type D personality was associated with decreased FMD across baseline, 3 months, and 12 months (mixed model analysis, p = 0.04), after adjustment for clinical characteristics, exercise training and depression. There was no significant association between Type D and decreased EPCs (p = 0.07). Age and smoking were other significant correlates of FMD and EPCs. Using a FMD <5.5% cut-off, Type D patients more often had endothelial dysfunction at baseline (24/37 = 65%) than non-Type Ds (63/143 = 44%); OR = 3.03, 95% CI 1.04-8.80. This significant Type D effect was confirmed in prospective analyses of endothelial dysfunction at 12 months (OR = 3.43, 95% CI 1.01-11.64), and in subgroup analyses of male patients. CONCLUSIONS: Type D personality was associated with impaired endothelial function in men with CAD. This association was robust across time, independent from depressive symptoms, and supports the notion that Type D has an adverse effect on cardiovascular health in patients with CAD.

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.

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.

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.