Exercise training and high-sensitivity cardiac troponin-I in patients with heart failure with reduced ejection fraction.

AIMS: The aims of this sub-study of the SMARTEX trial were (1) to evaluate the effects of a 12-week exercise training programme on serum levels of high sensitivity cardiac troponin I (hs-cTnI) in patients with moderate chronic heart failure (CHF), in New York Heart Association class II-III with reduced ejection fraction (HFrEF) and (2) to explore the associations with left ventricular remodelling, functional capacity and filling pressures measured with N-terminal pro brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: In this sub-study, 196 patients were randomly assigned to high intensity interval training (HIIT, n = 70), moderate continuous training (MCT, n = 59) or recommendation of regular exercise (RRE), (n = 67) for 12 weeks. To reveal potential difference between structured intervention and control, HIIT and MCT groups were merged and named supervised exercise training (SET) group. The RRE group constituted the control group (CG). To avoid contributing factors to myocardial injury, we also evaluated changes in patients without additional co-morbidities (atrial fibrillation, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease). The relationship between hs-cTnI and left ventricular end-diastolic diameter (LVEDD), VO2peak, and NT-proBNP was analysed by linear mixed models. At 12 weeks, Hs-cTnI levels were modestly but significantly reduced in the SET group from median 11.9 ng/L (interquartile ratio, IQR 7.1-21.8) to 11.5 ng/L (IQR 7.0-20.7), P = 0.030. There was no between-group difference (SET vs. CG, P = 0.116). There was a numerical but not significant reduction in hs-cTnI for the whole population (P = 0.067) after 12 weeks. For the sub-group of patients without additional co-morbidities, there was a significant between-group difference: SET group (delta -1.2 ng/L, IQR -2.7 to 0.1) versus CG (delta -0.1 ng/L, IQR -0.4 to 0.7), P = 0.007. In the SET group, hs-cTnI changed from 10.9 ng/L (IQR 6.0-22.7) to 9.2 ng/L (IQR 5.2-20.5) (P = 0.002), whereas there was no change in the CG (6.4 to 5.8 ng/L, P = 0.64). Changes in hs-cTnI (all patients) were significantly associated with changes in; LVEDD, VO2peak, and NT-proBNP, respectively. CONCLUSIONS: In patients with stable HFrEF, 12 weeks of structured exercise intervention was associated with a modest, but significant reduction of hs-cTnI. There was no significant difference between intervention group and control group. In the sub-group of patients without additional co-morbidities, this difference was highly significant. The alterations in hs-cTnI were associated with reduction of LVEDD and natriuretic peptide concentrations as well as improved functional capacity.

Aerobic high-intensity interval exercise training in patients with angina and no obstructive coronary artery disease: feasibility and physiological effects.

Aims: Patients with chest pain and normal coronary angiogram [angina with normal coronary arteries (ANOCA)] constitute a therapeutic problem with considerable functional limitation and reduced quality of life. The aims of the current pilot study were to (i) explore if a structured aerobic high-intensity interval training (HIT) program for 12 weeks was feasible in patients with ANOCA, and (ii) to assess mechanisms related to symptoms in this population. Methods and results: Sixteen patients with ANOCA underwent a 3-month aerobic HIT program with one-to-one monitored exercise sessions on treadmill in a 4 min × 4 manner, three times a week. Four patients served as controls. Coronary flow velocity reserve (CFVR) transthoracic Doppler, flow-mediated vasodilation (FMD) and VO2max was measured at baseline and after 12 weeks. The average attendance to training sessions was 82.3% ± 10.1 (56-94). CFVR in the training group increased from 2.50 ± 0.48 to 3.04 ± 0.71 (P < 0.001) whereas FMD increased from 4.19 ± 2.42% to 8.28 ± 2.85% (P < 0.001). Improvement in CFVR correlated with the relative improvement in FMD (R = 0.45, P = 0.047). This was associated with an increase in VO2max from 28.75 ± 6.51 mL/kg/min to 31.93 ± 6.46 mL/kg/min (P < 0.001). Conclusion: A 3-month program of monitored HIT was feasible, with high adherence resulting in improved functional capacity in patients with ANOCA. CFVR improved and this improvement was associated with improved FMD. ClinicalTrialsgov Identifier: NCT02905630.

Blood Lactate AUC Is a Sensitive Test for Evaluating the Effect of Exercise Training on Functional Work Capacity in Patients with Chronic Heart Failure.

PURPOSE: Exercise training is an essential treatment option for patients with chronic heart failure (CHF). However, it remains controversial, which surrogate measures of functional work capacity are most reliable. The purpose of this paper was to compare functional capacity work measured as capillary lactate concentrations area under the curve (AUC) with standard cardiopulmonary exercise testing (CPET) with VO2peak and the 6-minute walk test (6 MWT). METHODS: Twenty-three patients in New York Heart Association (NYHA) class II/III with left ventricular ejection fraction (LVEF) <35% were randomised to home-based recommendation of regular exercise (RRE) (controls), moderate continuous training (MCT) or aerobic interval training (AIT). The MCT and AIT groups underwent 12 weeks of supervised exercise training. Exercise testing was performed as standard CPET treadmill test with analysis of VO2peak, the 6 MWT and a novel 30-minute submaximal treadmill test with capillary lactate AUC. RESULTS: All patients had statistically significant improvements in VO2peak, 6 MWT and lactate AUC after 12 weeks of exercise training: 6 MWT (p =0.035), VO2peak (p =0.049) and lactate AUC (p =0.002). Lactate AUC (p =0.046) and 6MWT (p =0.035), but not VO2peak revealed difference between the exercise modalities regarding functional work capacity. CONCLUSION: 6-MWT and lactate AUC, but not VO2peak, were able to reveal a statistically significant improvement in functional capacity between different exercise modalities.

Exercise training and high-sensitivity cardiac troponin T in patients with heart failure with reduced ejection fraction.

AIMS: Whether an exercise training intervention is associated with reduction in long-term high-sensitivity cardiac troponin T (hs-cTnT) concentration (a biomarker of subclinical myocardial injury) in patients with heart failure with reduced ejection fraction (HFrEF) is unknown. The aims were to determine (i) the effect of a 12 week endurance exercise training intervention with different training intensities on hs-cTnT in stable patients with HFrEF (left ventricular ejection fraction ≤ 35%) and (ii) associations between hs-cTnT and peak oxygen uptake (VO2peak ). METHODS AND RESULTS: In this sub-study of the SMARTEX-HF trial originally including 261 patients from nine European centres, 213 eligible patients were included after withdrawals and appropriate exclusions [19% women, mean age 61.2 years (standard deviation: 11.9)], randomized to high-intensity interval training (HIIT; n = 77), moderate continuous training (MCT; n = 63), or a recommendation of regular exercise (RRE; n = 73). Hs-cTnT measurements and clinical data acquired before (BL) and after a 12 week exercise training intervention (12 weeks) and at 1 year follow-up (1 year) were analysed using multivariable mixed models. Baseline hs-cTnT was above the 99th percentile upper reference limit of 14 ng/L in 35 (48%), 35 (56%), and 49 (64%) patients in the RRE, MCT, and HIIT groups, respectively. Median hs-cTnT was 16 ng/L at BL, 14 ng/L at 12 weeks, and 14 ng/L at 1 year. Hs-cTnT was statistically significantly reduced at 12 weeks in a model adjusted for randomization group, centre and VO2peak , and after further adjustment in the final model that also included age, sex, creatinine concentrations, N-terminal pro-brain natriuretic peptide, smoking, and heart failure treatment. The mean reduction from BL to 12 weeks in the final model was 1.1 ng/L (95% confidence interval: 1.0-1.2 ng/L, P < 0.001), and the reduction was maintained at 1 year with a mean reduction from BL to 1 year of 1.1 ng/L (95% confidence interval: 1.0-1.1 ng/L, P = 0.025). Randomization group was not associated with hs-cTnT at any time point (overall test: P = 0.20, MCT vs. RRE: P = 0.81, HIIT vs. RRE: P = 0.095, interaction time × randomization group: P = 0.88). Independent of time point, higher VO2peak correlated with lower hs-cTnT (mean reduction over all time points: 0.2 ng/L per increasing mL·kg-1 ·min-1 , P = 0.002), without between-group differences (P = 0.19). CONCLUSIONS: In patients with stable HFrEF, a 12 week exercise intervention was associated with reduced hs-cTnT in all groups when adjusted for clinical variables. Higher VO2peak correlated with lower hs-cTnT, suggesting a positive long-term effect of increasing VO2peak on subclinical myocardial injury in HFrEF, independent of training programme.

Baseline and Exercise Predictors of V˙O2peak in Systolic Heart Failure Patients: Results from SMARTEX-HF.

PURPOSE: This study aimed to investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (V˙O2peak) from baseline to 12-wk follow-up (ΔV˙O2peak) in a post hoc analysis from the SMARTEX Heart Failure trial. METHODS: We studied 215 patients with heart failure with left ventricular ejection fraction (LVEF) ≤35%, and New York Heart Association (NYHA) classes II-III who were randomized to either supervised high-intensity interval training with exercise target intensity of 90%-95% of peak heart rate (HRpeak) or supervised moderate continuous training (MCT) with target intensity of 60%-70% of HRpeak, or who received a recommendation of regular exercise on their own. Predictors of ΔV˙O2peak were assessed in two models: a logistic regression model comparing highest and lowest tertiles (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters). RESULTS: The change in V˙O2peak in response to the interventions (ΔV˙O2peak) varied substantially, from -8.50 to +11.30 mL·kg·min. Baseline NYHA (class II gave higher odds vs III; odds ratio (OR), 7.1 (2.0-24.9); P = 0.002), LVEF (OR per percent, 1.1 (1.0-1.2); P = 0.005), and age (OR per 10 yr, 0.5 (0.3-0.8); P = 0.003) were associated with ΔV˙O2peak.In the multivariate linear regression, 34% of the variability in ΔV˙O2peak was explained by the increase in exercise training workload, ΔHRpeak between baseline and 12-wk posttesting, age, and ever having smoked. CONCLUSION: Exercise training response (ΔV˙O2peak) correlated negatively with age, LVEF, and NYHA class. The ability to increase workload during the training period and increased ΔHRpeak between baseline and the 12-wk test were associated with a positive outcome.

Impact of an exercise training program on cardiac neuronal function in heart failure patients on optimal medical therapy : A randomized Iodine-123 metaiodobenzylguanidine scintigraphy study.

BACKGROUND: The syndrome of heart failure (HF) is characterized by left ventricular dysfunction and a compensatory chronic over activation of the sympathetic nervous system. We wanted to investigate if the beneficial effects of exercise training (ET) in HF patients on optimal medical therapy (OMT) are associated with alterations in cardiac sympathetic activity. METHODS: Cardiac sympathetic activity was evaluated at baseline and after 12 weeks using metaiodobenzylguanidine scintigraphy in 23 patients with stable HF participating in the SmartEx trial. Patients with HF in New York Heart Association class II or III and left ventricular ejection fraction <35 % were randomized to three different ET groups. RESULTS: We found no statistically significant changes in cardiac sympathetic activity after 12 weeks of ET. Heart to mediastinum (H/M) ratio at 15 minutes (0.00174 ± 0.0841, P = 0.922), H/M ratio at 4 hours (-0.00565 ± 0.1163, P = 0.818) and washout ratio (WR) (-1.2666 ± 16.5412, P = 0.717). A further group-wise analysis of the three ET groups did not show any difference between the groups. CONCLUSION: A 12-week ET program did not alter the abnormal cardiac sympathetic activity in stable HF patients on modern OMT.

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). METHODS: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. RESULTS: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. CONCLUSIONS: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Confronting one's vulnerability - patients with chest pain participating in a high-intensity exercise programme.

AIMS AND OBJECTIVES: To explain the transitional process that individuals with unexplained chest pain undergo while participating in an exercise training programme over time. BACKGROUND: Angina-like chest pain in patients with no obstructive coronary artery disease is a growing problem. Functional limitations, restricted daily activities and reduced quality of life are reported. In addition, physical activity is avoided in this population. DESIGN: The study follows a qualitative classic grounded theory (Glaser ). METHODS: Three times a week for 12 weeks, twelve patients with no obstructive coronary artery disease participated in a high-intensity aerobic exercise training programme supervised by physiotherapists and nurses. The data collection was based on diaries and interviews about the experience and analysed according to the principles of classic grounded theory. RESULTS: The core category was identified as 'confronting one's vulnerability' and included three subcategories: 'balancing existential uncertainty', 'transforming bodily perceptions' and 'becoming a more capable person'. CONCLUSION: The transition was described as a process of becoming more capable. Health professionals should be aware of the significance of high-intensity exercise training for people with unexplained chest pain and of the underlying dimension of vulnerability. RELEVANCE TO CLINICAL PRACTICE: Understanding the transition process that people with unexplained chest pain undergo while participating in a high-intensity exercise training programme promotes a person-centred approach. Taking this substantive theory into consideration will improve the prerequisites for establishing person-centred care.

Aerobic interval training in patients with heart failure and an implantable cardioverter defibrillator: a controlled study evaluating feasibility and effect.

BACKGROUND: Aerobic interval training (AIT) has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with both coronary artery disease and heart failure (HF). The objective of this study was to evaluate this training modality in patients with HF and an implantable cardioverter defibrillator (ICD) with regard to feasibility, safety, and effect. METHODS: We prospectively included 38 patients with an ICD: 26 patients participated in an AIT programme for 3 months, while 12 patients served as controls. At baseline and 12-week follow up, patients were assessed with a maximal ergospirometry stress test, echocardiography, endothelial function testing, and ICD interrogation. RESULTS: No exercise-related adverse events occurred during or soon after the training sessions. ICD interrogation revealed no sustained arrhythmias, antitachycardia pacing, or ICD discharge related to exercise sessions. The AIT programme led to a significant increase in peak oxygen uptake, cycle ergometer workload, and endothelial function compared to the control group. The training programme was safe and not associated with any adverse events or ICD-related complications. CONCLUSIONS: An AIT programme is feasible and seems safe in a well-treated, stable ICD population. Further, AIT for 3 months results in significantly increased aerobic capacity and endothelial function in this population.

Response of growth differentiation factor-15 to percutaneous coronary intervention and regular exercise training.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is considered to be a cardioprotective cytokine possessing antiapoptotic and antiproliferative properties. If GDF-15 plasma levels are influenced by percutanenous coronary intervention (PCI) or regular exercise training is currently not known. METHODS: After successful revascularization by PCI with stent implantation 36 consecutive patients with stable angina pectoris were randomized to an exercise training program or to a control group. Patients were followed by serial measurements of GDF-15, high-sensitivity Troponin T (hsTNT) and N-terminal pro brain natriuretic peptide (NT-proBNP) levels in peripheral blood after PCI and during six months follow-up. RESULTS: Plasma levels of GDF-15 showed an early response to PCI with a modest, but significant increase after 30 minutes (p = 0.007) peaking three hours after PCI. Levels of hsTNT rose 5-fold from baseline to 24 hours (p < 0.001) with a normalization at seven days post PCI. Changes in plasma levels of GDF-15, hsTNT and NT-proBNP were not significantly different between the training and control group during follow-up. CONCLUSIONS: GDF-15 levels show a modest transient increase in response to coronary intervention with stent implantation. Exercise training over six months does not affect plasma levels of GDF-15, hsTNT or NT-proBNP in patients with stable coronary artery disease.