The relationship between workload and exercise-induced cardiac troponin elevations is influenced by non-obstructive coronary atherosclerosis.

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.

High dose statin treatment reduces circulating Dickkopf-1 following acute myocardial infarction.

BACKGROUND: Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known. METHODS: We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; n = 25) and moderate dose (20 mg simvastatin, given the day after PCI; n = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed. RESULTS: (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of ß-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. (iii) DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC. CONCLUSIONS: Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients.

Optimizing support vector machines and autoregressive integrated moving average methods for heart rate variability data correction.

Heart rate variability (HRV) is the variation in time between successive heartbeats and can be used as an indirect measure of autonomic nervous system (ANS) activity. During physical exercise, movement of the measuring device can cause artifacts in the HRV data, severely affecting the analysis of the HRV data. Current methods used for data artifact correction perform insufficiently when HRV is measured during exercise. In this paper we propose the use of autoregressive integrated moving average (ARIMA) and support vector regression (SVR) for HRV data artifact correction. Since both methods are only trained on previous data points, they can be applied not only for correction (i.e., gap filling), but also prediction (i.e., forecasting future values). Our paper describes:•why HRV is difficult to predict and why ARIMA and SVR might be valuable options.•finding the best hyperparameters for using ARIMA and SVR to correct HRV data, including which criterion to use for choosing the best model.•which correction method should be used given the data at hand.

Circulating trimethylamine N-oxide levels do not predict 10-year survival in patients with or without coronary heart disease.

BACKGROUND: Trimethylamine N-oxide (TMAO) is an amine oxide generated by gut microbial metabolism. TMAO may contribute to atherothrombosis and systemic inflammation. However, the prognostic value of circulating TMAO for risk stratification is uncertain. METHODS: We assessed prospective relationships of plasma TMAO with long-term risk of all-cause, cardiovascular (CV), and non-CV mortality in the Western Norway Coronary Angiography Cohort (WECAC; 4132 patients with suspected coronary artery disease) and the Hordaland Health Study (HUSK; 6393 community-based subjects). Risk associations were examined using Cox regression analyses. RESULTS: Mean follow-up was 9.8 and 10.5 years in WECAC and HUSK, respectively. Following adjustments for established CV risk factors and indices of renal function in WECAC, the hazard ratios (HRs) (95% confidence intervals [CIs]) per one standard deviation increase in log-transformed plasma TMAO were 1.04 (0.97-1.12), 1.06 (0.95-1.18), and 1.03 (0.93-1.13) for all-cause, CV, and non-CV mortality, respectively. Essentially similar results were obtained in patients with angiographically significant coronary artery disease and patients with reduced left ventricular ejection fraction. Corresponding HRs (95% CIs) in the HUSK cohort were 1.03 (0.96-1.10), 1.01 (0.89-1.13), and 1.03 (0.95-1.12) for all-cause-, CV, and non-CV mortality, respectively. CONCLUSIONS: Circulating TMAO did not predict long-term all-cause, CV, or non-CV mortality in patients with coronary heart disease or in community-based adults. This large study does not support a role of TMAO for patient risk stratification in primary or secondary prevention.

Cardiac Structure and Function in Epilepsy Patients with Drug-Resistant Convulsive Seizures.

High frequency of convulsive seizures and long-lasting epilepsy are associated with an increased risk of sudden unexpected death in epilepsy (SUDEP). Structural changes in the myocardium have been described in SUDEP victims. It is speculated that these changes are secondary to frequent convulsive seizures and may predispose to SUDEP. The aim of this cross-sectional study was to investigate the impact of chronic drug-resistant epilepsy on cardiac function and structure in patients with a high frequency of convulsive seizures. We consecutively included 21 patients (17 women, 4 men) aged 18-40 years, with at least 10 years with epilepsy and a minimum of six convulsive seizures in the last year and without a history of status epilepticus or nonepileptic events. A complete clinical examination, resting 12-lead electrocardiogram, 72-h Holter monitoring, and echocardiography were recorded in all patients. Ten patients were assessed by 3-Tesla cardiac magnetic resonance imaging. Echocardiography and MRI data were compared with those from age- and sex-matched healthy control individuals. No significant changes in cardiac structure or function were found among patients with chronic drug-resistant epilepsy and high frequency of convulsive seizures. However, we cannot exclude that there are subgroups of patients who are more prone to epilepsy-associated cardiac alterations.

The Association of Smoking with Hospitalization and Mortality Differs According to Sex in Patients with Heart Failure Following Myocardial Infarction.

Background: Smoking has been associated with higher morbidity and mortality following myocardial infarction (MI), but reports of the impact on morbidity and mortality for females and elderly patients experiencing MI complicated with left ventricular dysfunction or overt heart failure are limited. Materials and Methods: In an individual patient data meta-analysis of high-risk MI patients, the association of smoking with hospitalizations and death were investigated. Weighted Cox proportional hazard modeling were used to study the risks of smoking on adjudicated endpoints among different sex and age categories. Results: Twenty-eight thousand seven hundred thirty-five patients from the CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT trials were assessed. After weighting, smokers (N = 18,148) were unfrequently women (29.2%) and a minority were above ≥80 years (9.8%). Smoking was significantly more associated with all-cause hospitalizations in women (hazard ratio [HR] 1.24; 95% confidence interval [95% CI] 1.16-1.32) than in men (HR = 1.10; 95% CI 1.05-1.16) resulting in a significant interaction between smoking and sex (p = 0.005). Smoking was predictive of all-cause mortality homogenously across age categories (p for interaction = 0.25) and sex (p for interaction = 0.58). Conclusions: The influence of smoking on morbidity differed according to sex following high-risk MI. The deleterious impact of smoking on hospitalization appeared particularly potent in women, which should further reinforce preventive strategies in females.

Myocardial inefficiency is an early indicator of exercise-induced myocardial fatigue.

Background: The effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue. Materials and methods: LV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress. Results: 59 healthy recreational athletes, 52 (43-59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p < 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p < 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003). Conclusion: Increased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.

Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance.

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.

Texture-based probability mapping for automatic scar assessment in late gadolinium-enhanced cardiovascular magnetic resonance images.

PURPOSE: To evaluate a novel texture-based probability mapping (TPM) method for scar size estimation in LGE-CMRI. METHODS: This retrospective proof-of-concept study included chronic myocardial scars from 52 patients. The TPM was compared with three signal intensity-based methods: manual segmentation, full-width-half-maximum (FWHM), and 5-standard deviation (5-SD). TPM is generated using machine learning techniques, expressing the probability of scarring in pixels. The probability is derived by comparing the texture of the 3 × 3 pixel matrix surrounding each pixel with reference dictionaries from patients with established myocardial scars. The Sørensen-Dice coefficient was used to find the optimal TPM range. A non-parametric test was used to test the correlation between infarct size and remodeling parameters. Bland-Altman plots were performed to assess agreement among the methods. RESULTS: The study included 52 patients (76.9% male; median age 64.5 years (54, 72.5)). A TPM range of 0.328-1.0 was found to be the optimal probability interval to predict scar size compared to manual segmentation, median dice (25th and 75th percentiles)): 0.69(0.42-0.81). There was no significant difference in the scar size between TPM and 5-SD. However, both 5-SD and TPM yielded larger scar sizes compared with FWHM (p < 0.001 and p = 0.002). There were strong correlations between scar size measured by TPM, and left ventricular ejection fraction (LVEF, r = -0.76, p < 0.001), left ventricular end-diastolic volume index (r = 0.73, p < 0.001), and left ventricular end-systolic volume index (r = 0.75, p < 0.001). CONCLUSION: The TPM method is comparable with current SI-based methods, both for the scar size assessment and the relationship with left ventricular remodeling when applied on LGE-CMRI.

Determinants of Interindividual Variation in Exercise-Induced Cardiac Troponin I Levels.

Background Postexercise cardiac troponin levels show considerable interindividual variations. This study aimed to identify the major determinants of this postexercise variation in cardiac troponin I (cTnI) following 3 episodes of prolonged high-intensity endurance exercise. Methods and Results Study subjects were recruited among prior participants in a study of recreational cyclists completing a 91-km mountain bike race in either 2013 or 2014 (first race). In 2018, study participants completed a cardiopulmonary exercise test 2 to 3 weeks before renewed participation in the same race (second race). Blood was sampled before and at 3 and 24 hours following all exercises. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Fifty-nine individuals (aged 50±9 years, 13 women) without cardiovascular disease were included. Troponin values were lowest before, highest at 3 hours, and declining at 24 hours. The largest cTnI difference was at 3 hours following exercise between the most (first race) (cTnI: 200 [87-300] ng/L) and the least strenuous exercise (cardiopulmonary exercise test) (cTnI: 12 [7-23] ng/L; P<0.001). The strongest correlation between troponin values at corresponding times was before exercise (r=0.92, P<0.0001). The strongest correlations at 3 hours were between the 2 races (r=0.72, P<0.001) and at 24 hours between the cardiopulmonary exercise test and the second race (r=0.83, P<0.001). Participants with the highest or lowest cTnI levels showed no differences in race performance or baseline echocardiographic parameters. Conclusions The variation in exercise-induced cTnI elevation is largely determined by a unique individual cTnI response that is dependent on the duration of high-intensity exercise and the timing of cTnI sampling. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Regular consumption of cod liver oil is associated with reduced basal and exercise-induced C-reactive protein levels; a prospective observational trial : A NEEDED (The North Sea Race Endurance Exercise Study) 2014 sub-study.

BACKGROUND: Dietary supplement use among recreational athletes is common, with the intention of reducing inflammation and improving recovery. We aimed to describe the relationship between omega-3 fatty acid supplement use and inflammation induced by strenuous exercise. METHODS: C-reactive protein (CRP) concentrations were measured in 1002 healthy recreational athletes before and 24 h after a 91-km bicycle race. The use of omega-3 fatty acid supplements was reported in 856 out of 1002 recreational athletes, and the association between supplement use and the exercise-induced CRP response was assessed. RESULTS: Two hundred seventy-four subjects reported regular use of omega-3 fatty acid supplements. One hundred seventy-three of these used cod liver oil (CLO). Regular users of omega-3 fatty acid supplements had significantly lower basal and exercise-induced CRP levels as compared to non-users (n = 348, p < 0.001). Compared to non-users, regular users had a 27% (95% confidence interval (CI): 14-40) reduction in Ln CRP response (unadjusted model, p < 0.001) and 16% (95% CI: 5-28, p = 0.006) reduction after adjusting for age, sex, race duration, body mass index, delta creatine kinase, MET hours per week, resting heart rate and higher education. CLO was the primary driver of this response with a 34% (95% CI: 19-49) reduction (unadjusted model, p < 0.001) compared to non-users. Corresponding numbers in the adjusted model were 24% (95% CI: 11-38, p < 0.001). CONCLUSION: Basal CRP levels were reduced, and the exercise-induced CRP response was attenuated in healthy recreational cyclists who used omega-3 fatty acid supplements regularly. This effect was only present in regular users of CLO. TRIAL REGISTRATION: NCT02166216 , registered June 18, 2014 - Retrospectively registered.

The relationship between Fibroblast Growth Factor 23 (FGF23) and cardiac MRI findings following primary PCI in patients with acute first time STEMI.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a regulator of mineral metabolism, that has been linked to myocardial remodeling including development of left ventricular (LV) hypertrophy and myocardial fibrosis. The aim of this study was to investigate the relationship between intact FGF23 (iFGF23), myocardial infarct size and LV remodeling following a first acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Forty-two consecutive patients with first-time STEMI, single vessel disease, successfully treated with primary percutaneous coronary intervention were included. Cardiac magnetic resonance (CMR) imaging was performed at day 2, 1 week, 2 months and 1 year post MI, and blood samples were drawn at admittance and at the same time points as the CMRs. The cohort was divided according to the presence or not of heart failure post MI. In the total cohort, iFGF23 (mean ± SD) was significantly lower at day 0 (33.7 ± 20.6 pg/ml) and day 2 (31.5 ± 23.4 pg/ml) compared with a reference interval based on 8 healthy adults (43.9 pg/ml ± 19.0 pg/ml). iFGF23 increased to normal levels (55.8 ± 23.4 pg/ml) seven days post MI. In the subset of patients with signs of acute heart failure, FGF23 was higher at all measured timepoints, reaching significantly higher FGF23 levels at 2 months and 1 year following revascularization. CONCLUSION: There was a reduction in iFGF23 levels during the acute phase of MI, with a normalization at seven days following revascularization. During one-year follow-up, there was a gradual increase in iFGF23 levels in patients with heart failure.

Trimethyllysine predicts all-cause and cardiovascular mortality in community-dwelling adults and patients with coronary heart disease.

Aims: Trimethyllysine (TML) is involved in carnitine synthesis, serves as a precursor of trimethylamine N-oxide (TMAO) and is associated with cardiovascular events in patients with established coronary heart disease (CHD). We prospectively examined circulating TML as a predictor of all-cause and cardiovascular mortality in community-dwelling adults and patients with CHD. Methods and results: By Cox regression modelling, risk associations were examined in 6393 subjects in the community-based Hordaland Health Study (HUSK). A replication study was conducted among 4117 patients with suspected stable angina pectoris in the Western Norway Coronary Angiography Cohort (WECAC). During a mean follow-up of 10.5 years in the HUSK-cohort, 884 (13.8%) subjects died, of whom 287 from cardiovascular causes. After multivariable adjustments for traditional cardiovascular risk factors, the hazard ratio (HR) [95% confidence interval (95% CI)] for all-cause mortality comparing the 4th vs. 1st TML-quartile was 1.66 (1.31-2.10, P < 0.001). Particularly strong associations were observed for cardiovascular mortality [HR (95% CI) 2.04 (1.32-3.15, P = 0.001)]. Corresponding risk-estimates in the WECAC (mean follow-up of 9.8 years) were 1.35 [1.10-1.66, P = 0.004] for all-cause and 1.45 [1.06-1.98, P = 0.02] for cardiovascular mortality. Significant correlations between plasma TML and TMAO were observed in both cohorts (rs ≥ 0.42, P < 0.001); however, additional adjustments for TMAO did not materially influence the risk associations, and no effect modification by TMAO was found. Conclusions: Elevated TML-levels were associated with increased risk of all-cause and cardiovascular mortality both in subjects with and without established CHD.

Artifact Correction in Short-Term HRV during Strenuous Physical Exercise.

Heart rate variability (HRV) analysis can be a useful tool to detect underlying heart or even general health problems. Currently, such analysis is usually performed in controlled or semi-controlled conditions. Since many of the typical HRV measures are sensitive to data quality, manual artifact correction is common in literature, both as an exclusive method or in addition to various filters. With proliferation of Personal Monitoring Devices with continuous HRV analysis an opportunity opens for HRV analysis in a new setting. However, current artifact correction approaches have several limitations that hamper the analysis of real-life HRV data. To address this issue we propose an algorithm for automated artifact correction that has a minimal impact on HRV measures, but can handle more artifacts than existing solutions. We verify this algorithm based on two datasets. One collected during a recreational bicycle race and another one in a laboratory, both using a PMD in form of a GPS watch. Data include direct measurement of electrical myocardial signals using chest straps and direct measurements of power using a crank sensor (in case of race dataset), both paired with the watch. Early results suggest that the algorithm can correct more artifacts than existing solutions without a need for manual support or parameter tuning. At the same time, the error introduced to HRV measures for peak correction and shorter gaps is similar to the best existing solution (Kubios-inspired threshold-based cubic interpolation) and better than commonly used median filter. For longer gaps, cubic interpolation can in some cases result in lower error in HRV measures, but the shape of the curve it generates matches ground truth worse than our algorithm. It might suggest that further development of the proposed algorithm may also improve these results.

High-Sensitivity Cardiac Troponin I and T Response Following Strenuous Activity is Attenuated by Smokeless Tobacco: NEEDED (North Sea Race Endurance Exercise Study) 2014.

Background Use of snus, a smokeless tobacco product, is increasing in Scandinavia. Strenuous physical activity is associated with an acute increase in high-sensitivity cardiac troponin (swhs-cTn) concentrations. Current smoking is associated with lower hs-cTn, but whether this also holds true for smokeless tobacco and whether tobacco affects the hs-cTn response to exercise remain unknown. Methods and Results We measured hs-cTnI and hs-cTnT concentrations in 914 recreational athletes before and 3 and 24 hours after a 91-km bicycle race. Self-reported snus tobacco habits were reported as noncurrent (n=796) and current (n=118). The association between snus use and change in log-transformed hs-cTnI and hs-cTnT concentrations (ie, the differences between concentrations at baseline and 3 hours and 24 hours ) were assessed by multivariable linear regression analysis. Concentrations of hs-cTn at baseline were lower in current than in noncurrent snus users (hs-cTnI median, 1.7 ng/L; Q1 to Q3: 1.6-2.3 versus 2.0 ng/L; Q1 to Q3: 1.6-3.2 [P=0.020]; and hs-cTnT: median, 2.9 ng/L, Q1 to Q3: 2.9-3.5 versus 2.9 ng/L, Q1 to Q3: 2.9-4.3 [P=0.021]). In fully adjusted multivariable models, use of snus was associated with lower change in hs-cTn concentrations from baseline to 3 hours (hs-cTnI: -29% [P=0.002], hs-cTnT: -18% [P=0.010]) and 24 hours (hscTnI: -30% [P=0.010], hs-cTnT -19%, [P=0.013]). Conclusions Resting hs-cTn concentrations are lower and the exercise-induced cardiac troponin response is attenuated in current users of smokeless tobacco compared with nonusers. Further insight into the pathophysiological processes underlying the attenuated cardiac troponin response to exercise in tobacco users is needed. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02166216.

Methods for preprocessing time and distance series data from personal monitoring devices.

There is a need to develop more advanced tools to improve guidance on physical exercise to reduce risk of adverse events and improve benefits of exercise. Vast amounts of data are generated continuously by Personal Monitoring Devices (PMDs) from sports events, biomedical experiments, and fitness self-monitoring that may be used to guide physical exercise. Most of these data are sampled as time- or distance-series. However, the inherent high-dimensionality of exercise data is a challenge during processing. As a result, current data analysis from PMDs seldomly extends beyond aggregates. Common challanges are:•alterations in data density comparing the time- and the distance domain;•large intra and interindividual variations in the relationship between numerical data and physiological properties;•alterations in temporal statistical properties of data derived from exercise of different exercise durations. These challenges are currently unresolved leading to suboptimal analytic models. In this paper, we present algorithms and approaches to address these problems, allowing the analysis of complete PMD datasets, rather than having to rely on cumulative statistics. Our suggested approaches permit effective application of established Symbolic Aggregate Approximation modeling and newer deep learning models, such as LSTM.

6 min walk test is a strong independent predictor of death in outpatients with heart failure.

AIMS: The aim of this study was to examine the prognostic value of the 6 min walk test (6MWT) in a large cohort of outpatients with heart failure. METHODS AND RESULTS: A total of 5519 outpatients with heart failure from the National Norwegian Heart Failure Registry (NNHFR), which is part of the Norwegian Cardiovascular Disease Registry, were included in this analysis. The NNHFR recommended the use of the 6MWT for prognostic assessment of all patients included in the registry. Patients were categorized according to the 6MWT: Category 1 walked the longest and Category 3 the shortest. During a median (25th-75th percentiles) follow-up of 24 (14-36), 12.9% of the patients died. Patients in Category 3 had the overall worst outcome than had patients in Categories 1 and 2. 6MWT used as a continuous variable was a highly significant independent predictor for mortality in a multivariate Cox regression model adjusted for 16 other variables with a hazard ratio of 0.979 [(95% confidence interval 0.972-0.986), P < 0.001]. The four most important predictors for mortality were active cancer in the last 5 years, age, 6MWT, and natriuretic peptides (all P < 0.001). CONCLUSIONS: 6MWT is a strong independent predictor of mortality in outpatients with HF. The findings support the use of the 6MWT in the prognostic assessment of patients with HF irrespective of HF aetiology.

Endurance exercise training volume is not associated with progression of coronary artery calcification.

BACKGROUND: Recent cross-sectional studies have suggested a dose-dependent relationship between lifelong exposure to physical activity and the burden of calcified coronary artery disease (CAD). No longitudinal studies have addressed this concern. HYPOTHESIS: Exercise volume is associated with progression of coronary artery calcium (CAC), defined as ≥10 units increase in CAC score. METHODS: Sixty-one recreational athletes who were assessed by coronary computed tomography angiography (CCTA) as part of the NEEDED 2013/14 study were re-assessed 4-5 years later, in 2018. RESULTS: Subjects were 45.9 ± 9.6 years old at inclusion, and 46 (74%) were male. Between 2013 and 2018, the participants reported median 5 (range: 0-20, 25th-75th percentile: 4-6) hours of high-intensity exercise per week. None of the included subjects smoked during follow-up. At inclusion, 21 (33%) participants had coronary artery calcifications. On follow-up CCTA in 2018, 15 (25%) subjects had progressive coronary calcification (≥10 Agatston units increase in CAC). These subjects were older (53 ± 9 vs 44 ± 9 years old, P = .002) and had higher levels of low-density lipoprotein at baseline (3.5 (2.9-4.3) vs 2.9 (2.3-3.5) mmol/L, P = .031) as compared to subjects with stable condition. No relationship was found between hours of endurance training per week and progression of coronary artery calcification. In multiple regression analysis, age and baseline CAC were the only significant predictors of progressive CAC. CONCLUSION: No relationship between exercise training volume and the progression of coronary artery calcification was found in this longitudinal study of middle-aged recreational athletes.