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.publishedVersio

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.publishedVersio

Plasma tumour necrosis factor correlates with mRNA expression of tumour necrosis factor and mitochondrial transcription factors in skeletal muscle in patients with chronic heart failure treated with cardiac resynchronization therapy: potential role in myopathy

Chronic heart failure (CHF) is characterized by inflammation and skeletal muscle myopathy, including impaired fibre type distribution and reduced capillary density, reduced cytochrome oxidase activity and reduced mitochondrial density. The myopathy is associated with activation of the interleukin-6–C-reactive protein pathway and the prototypical inflammatory cytokine tumour necrosis factor (TNF) with alterations in the mRNA expression of enzymes essential in mitochondrial biogenesis. Central in this process are peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide adenine dinucleotide and mitochondrial transcription factor (TFAM). The covariance over time between plasma levels of TNF and skeletal muscle mRNA expression of this pro-inflammatory cytokine, and the correlation between TNF and mRNA expression of enzymes essential in mitochondrial biogenesis and skeletal muscle pathology has not previously been evaluated in patients with CHF on stable medical treatment. The methods have been described previously and are briefly presented here.acceptedVersio

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

Plasma cell disorders (PCDs) are identified in the clinical lab by detecting the monoclonal immunoglobulin (M-protein) which they produce. Traditionally, serum protein electrophoresis methods have been utilized to detect and isotype Mproteins. Increasing demands to detect low-level disease and new therapeutic monoclonal immunoglobulin treatments have stretched the electrophoretic methods to their analytical limits. Newer techniques based on mass spectrometry (MS) are emerging which have improved clinical and analytical performance. MS is gaining traction into clinical laboratories, and has replaced immunofixation electrophoresis (IFE) in routine practice at one institution. The International Myeloma Working Group (IMWG) Mass Spectrometry Committee reviewed the literature in order to summarize current data and to make recommendations regarding the role of mass spectrometric methods in diagnosing and monitoring patients with myeloma and related disorders. Current literature demonstrates that immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS has clinical characteristics equivalent in performance to IFE with added benefits of detecting additional risk factors for PCDs, differentiating Mprotein from therapeutic antibodies, and is a suitable replacement for IFE for diagnosing and monitoring multiple myeloma and related PCDs. In this paper we discuss the IMWG recommendations for the use of MS in PCDs.publishedVersio

Baseline and exercise predictors of VO2peak in systolic heart failure patients : Results from SMARTEX-HF

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by American College of Sports Medicine in Medicine & Science in Sports & Exercise on 04/11/2019.Available online: https://journals.lww.com/acsm-msse/FullText/2020/04000/Baseline_and_Exercise_Predictors_of_V_O2peak_in.5.aspxacceptedVersio

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

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

Plasma cell disorders (PCDs) are identified in the clinical lab by detecting the monoclonal immunoglobulin (M-protein) which they produce. Traditionally, serum protein electrophoresis methods have been utilized to detect and isotype Mproteins. Increasing demands to detect low-level disease and new therapeutic monoclonal immunoglobulin treatments have stretched the electrophoretic methods to their analytical limits. Newer techniques based on mass spectrometry (MS) are emerging which have improved clinical and analytical performance. MS is gaining traction into clinical laboratories, and has replaced immunofixation electrophoresis (IFE) in routine practice at one institution. The International Myeloma Working Group (IMWG) Mass Spectrometry Committee reviewed the literature in order to summarize current data and to make recommendations regarding the role of mass spectrometric methods in diagnosing and monitoring patients with myeloma and related disorders. Current literature demonstrates that immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS has clinical characteristics equivalent in performance to IFE with added benefits of detecting additional risk factors for PCDs, differentiating Mprotein from therapeutic antibodies, and is a suitable replacement for IFE for diagnosing and monitoring multiple myeloma and related PCDs. In this paper we discuss the IMWG recommendations for the use of MS in PCDs

Baseline and Exercise Predictors of VO2peak in Systolic Heart Failure Patients: Results from SMARTEX-HF

Purpose To investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (VO2peak) from baseline to 12-week follow-up (ΔVO2peak) 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 NYHA class II-III, who were randomized to either supervised high intensity interval training (HIIT) with exercise target intensity 90-95% of peak heart rate (HRpeak), supervised moderate continuous training (MCT) with target intensity 60-70% of HRpeak, or who received a recommendation of regular exercise on their own (RRE). Predictors of ΔVO2peak were assessed in two models; A logistic regression model comparing highest and lowest tertile (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters). Results The change in VO2peak in response to the interventions (ΔVO2peak) varied substantially, from -8.50 to +11.30 mL·kg-1·min-1. Baseline NYHA (class II gave higher odds vs III, odds ratio (OR) 7.1 (2.0, 24.9), p=0.002), LVEF OR per % 1.1 (1.0, 1.2), p = 0.005), age (OR per 10 years 0.5 (0.3, 0.8)), p=0.003) were associated with ΔVO2peak. In the multivariate linear regression, 34% of the variability in [INCREMENT]VO2peak was explained by the increase in exercise training workload, [INCREMENT]HRpeak between baseline and 12-wk post-testing, age, and ever having smoked. Conclusion Exercise training response (ΔVO2peak) 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-week test were associated with a positive outcome