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.

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.

Perioperative Factors Associated With Changes in Troponin T During Coronary Artery Bypass Grafting.

OBJECTIVE: Investigate important clinical and operative variables associated with increases in cardiac troponin T (cTnT) as indicators of myocardial injury after coronary artery bypass grafting (CABG). DESIGN: Prospective cohort study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 626 patients undergoing isolated CABG from April 2008 through April 2010 with a validation cohort (n = 686) from 2015-2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Perioperative variables were registered prospectively. The extent of diffuse coronary atherosclerosis and significant stenoses were assessed with preoperative coronary angiography. Mixed model analysis was used to construct a statistical model explaining the course of cTnT concentrations. The model was adjusted for preoperative and intraoperative/postoperative myocardial infarction (MI) for independent assessment of additional variables. Clinical factors associated with increased cTnT concentrations during and after CABG were longer duration of cardiopulmonary bypass (p < 0.001), higher preoperative creatinine (p < 0.001), New York Heart Association functional classification IV (p = 0.006), reduced LVEF (p = 0.034), higher preoperative C-reactive protein (p = 0.049), and intraoperative/postoperative MI (p < 0.001). Factors associated with decreasing cTnT concentrations during CABG were higher BSA (p < 0.001) and a recent preoperative MI (p < 0.001). The extent of diffuse coronary atherosclerosis and significant stenoses were not associated with changes in cTnT (p = 0.35). Results were similar in the validation cohort. CONCLUSIONS: Left ventricular ejection fraction, New York Heart Association classification, kidney function, inflammation status, duration of cardiopulmonary bypass, body surface area, and preoperative MI were associated with the cTnT rise-and-fall pattern related to myocardial injury after CABG. Information regarding these variables may be valuable when using cTnT in the diagnostic workup of postoperative MI.