Cardiometabolic and immune response to exercise training in patients with metabolic syndrome: retrospective analysis of two randomized clinical trials.

Background: Metabolic syndrome (MetS) is defined by the presence of central obesity plus ≥two metabolic/cardiovascular risk factors (RF), with inflammation being a major disease-driving mechanism. Structured endurance exercise training (ET) may positively affect these traits, as well as cardiorespiratory fitness (V̇O2peak). Aims: We explore individual ET-mediated improvements of MetS-associated RF in relation to improvements in V̇O2peak and inflammatory profile. Methods: MetS patients from two randomized controlled trials, ExMET (n = 24) and OptimEx (n = 34), had performed 4- or 3-months supervised ET programs according to the respective trial protocol. V̇O2peak, MetS-defining RFs (both RCTs), broad blood leukocyte profile, cytokines and plasma proteins (ExMET only) were assessed at baseline and follow-up. Intra-individual changes in RFs were analysed for both trials separately using non-parametric approaches. Associations between changes in each RF over the exercise period (n-fold of baseline values) were correlated using a non-parametrical approach (Spearman). RF clustering was explored by uniform manifold approximation and projection (UMAP) and changes in RF depending on other RF or exercise parameters were explored by recursive partitioning. Results: Four months of ET reduced circulating leukocyte counts (63.5% of baseline, P = 8.0e-6), especially effector subtypes. ET response of MetS-associated RFs differed depending on patients' individual RF constellation, but was not associated with individual change in V̇O2peak. Blood pressure lowering depended on cumulative exercise duration (ExMET: ≥102 min per week; OptimEx-MetS: ≥38 min per session) and baseline triglyceride levels (ExMET: <150 mg/dl; OptimEx-MetS: <174.8 mg/dl). Neuropilin-1 plasma levels were inversely associated with fasting plasma triglycerides (R: -0.4, P = 0.004) and changes of both parameters during the ET phase were inversely correlated (R: -0.7, P = 0.0001). Conclusions: ET significantly lowered effector leukocyte blood counts. The improvement of MetS-associated cardiovascular RFs depended on individual basal RF profile and exercise duration but was not associated with exercise-mediated increase in V̇O2peak. Neuropilin-1 may be linked to exercise-mediated triglyceride lowering.

Prevalence and pattern of focal and potential diffuse myocardial fibrosis in male and female marathon runners using contrast-enhanced cardiac magnetic resonance.

OBJECTIVES: This study analyzed the prevalence and pattern of focal and potential diffuse myocardial fibrosis detected by late gadolinium enhancement (LGE) and extracellular volume (ECV) imaging in male and female marathon runners using cardiac magnetic resonance (CMR). METHODS: Seventy-four marathon runners were studied including 55 males (44 ± 8 years) and 19 females (36 ± 7 years) and compared to 36 controls with similar age and sex using contrast-enhanced CMR, exercise testing, and blood samples. RESULTS: Contrast-enhanced CMR revealed focal myocardial fibrosis in 8 of 74 runners (11%). The majority of runners were male (7 of 8, 88%). LGE was typically non-ischemic in 7 of 8 runners (88%) and ischemic in one runner. ECV was higher in remote myocardium without LGE in male runners (25.5 ± 2.3%) compared to male controls (24.0 ± 3.0%, p < 0.05), indicating the potential presence of diffuse myocardial fibrosis. LV mass was higher in LGE + males (86 ± 18 g/m2) compared to LGE- males (73 ± 14 g/m2, p < 0.05). Furthermore, LGE + males had lower weight (69 ± 9 vs 77 ± 9 kg, p < 0.05) and shorter best marathon finishing times (3.2 ± 0.3 h) compared to LGE- males (3.6 ± 0.4 h, p < 0.05) suggesting higher training load in these runners to accomplish the marathon in a short time. CONCLUSION: The high frequency of non-ischemic myocardial fibrosis in LGE + male runners can be related to increased LV mass in these runners. Furthermore, a higher training load could explain the higher LV mass and could be one additional cofactor in the genesis of myocardial fibrosis in marathon runners. KEY POINTS: • A high frequency of myocardial fibrosis was found in marathon runners. • Myocardial fibrosis occurred typically in male runners and was typically non-ischemic. • Higher training load could be one cofactor in the genesis of myocardial fibrosis in marathon runners.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 2.

BACKGROUND: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. METHODS: Generation of evidence and search of literature have been described in part 1. RESULTS: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. CONCLUSIONS: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.

Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology.

This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals. Valvular heart disease is usually an age-related degenerative process, predominantly affecting individuals in their fifth decade and onwards. However, there is an increasing group of younger individuals with valvular defects. The diagnosis of cardiac disorders during routine cardiac examination often raises questions about on-going participation in competitive sport with a high dynamic or static component and the level of permissible physical effort during recreational exercise. Although the natural history of several valvular diseases has been reported in the general population, little is known about the potential influence of chronic intensive physical activity on valve function, left ventricular remodelling pulmonary artery pressure, and risk of arrhythmia. Due to the sparsity of data on the effects of exercise on VHD, the present document is largely based on clinical experience and expert opinion.

Long-term Cardiac Maintenance Programming: A SINGLE-SITE ANALYSIS OF MORE THAN 200 PARTICIPANTS.

PURPOSE: Greater than 65% of all cardiac mortality is related to coronary artery disease (CAD). Cardiac rehabilitation (CR) aims to reduce cardiovascular risk and number of hospital readmissions. Cardiac maintenance programs (CMPs) are designed to sustain or improve health after completing early CR. Although CMPs are supported by most national health guidelines, few long-term studies on these diverse programs have been performed. METHODS: This was a retrospective repeated-measures analysis with case-controlled subanalysis. Within-subject differences for CMP participants were examined between enrollment and last clinical visit. Assessments included medical history, anthropometry, blood analysis, and cardiopulmonary exercise testing. A subset of 20 CMP participants were compared with 20 patients with CAD who chose not to participate in CMP, matched for age, sex, and follow-up duration. RESULTS: A total of 207 patients (60 ± 9 yr, 16% female) were included for the primary analyses. Average follow-up was 6.3 ± 4.8 yr (range 4-20 yr). CMP participants reduced peak workload (1.76 ± 0.56 to 1.60 ± 0.58 W/kg; P < .001) and aerobic capacity (26.1 ± 6.2 to 24.6 ± 7.1 mL/kg/min; P = .003). High-density lipoprotein-cholesterol increased significantly (48 ± 12 to 51 ± 14 mg/dL; P < .001), whereas all other metabolic risk factors remained unaffected. Matched controls had higher functional capacity (2.35 ± 0.81 vs 1.56 ± 0.52 W/kg; P < .001) and lower body mass index (25.3 ± 3.6 vs 28.6 ± 3.9 kg/m2) at baseline, but no significant differences with respect to long-term efficacy were observed. CONCLUSIONS: Long-term participation in CMP did not result in maintaining functional capacity or cardiovascular risk profile in patients with CAD. However, compared with matched nonparticipants, CMP participants (are more deconditioned at baseline) but do not seem to deteriorate as quickly.

Brief recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC).

This paper presents a brief summary of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology (EAPC) on sports-participation in patients with coronary artery disease, coronary artery anomalies or spontaneous dissection of the coronary arteries, all entities being associated with myocardial ischaemia.1 Given the wealth of evidence supporting the benefits of exercise for primary and secondary prevention of coronary artery disease, individuals should be restricted from competitive sport only when a substantial risk of adverse event or disease progression is present. These recommendations aim to encourage regular physical activity including participation in sports and, with reasonable precaution, ensure a high level of safety for all individuals with coronary artery disease. The present document is based on available current evidence, but in most instances because of lack of evidence, also on clinical experience and expert opinion.

Acute impact of an endurance race on cardiac function and biomarkers of myocardial injury in triathletes with and without myocardial fibrosis.

AIMS: The aim of this study was to investigate the occurrence of myocardial injury and cardiac dysfunction after an endurance race by biomarkers and cardiac magnetic resonance in triathletes with and without myocardial fibrosis. METHODS AND RESULTS: Thirty asymptomatic male triathletes (45 ± 10 years) with over 10 training hours per week and 55 ± 8 ml/kg per minute maximal oxygen uptake during exercise testing were studied before (baseline) and 2.4 ± 1.1 hours post-race. Baseline cardiac magnetic resonance included cine, T1/T2, late gadolinium enhancement (LGE) and extracellular volume imaging. Post-race non-contrast cardiac magnetic resonance included cine and T1/T2 mapping. Non-ischaemic myocardial fibrosis was present in 10 triathletes (LGE+) whereas 20 had no fibrosis (LGE-). At baseline, LGE + triathletes had higher peak exercise systolic blood pressure with 222 ± 21 mmHg compared to LGE- triathletes (192 ± 30 mmHg, P < 0.01). Post-race troponin T and creatine kinase MB were similarly increased in both groups, but there was no change in T2 and T1 from baseline to post-race with 54 ± 3 ms versus 53 ± 3 ms (P = 0.797) and 989 ± 21 ms versus 989 ± 28 ms (P = 0.926), respectively. However, post-race left atrial ejection fraction was significantly lower in LGE + triathletes compared to LGE- triathletes (53 ± 6% vs. 59 ± 6%, P < 0.05). Furthermore, baseline atrial peak filling rates were lower in LGE - triathletes (121 ± 30 ml/s/m2) compared to LGE + triathletes (161 ± 34 ml/s/m2, P < 0.01). Post-race atrial peak filling rates increased in LGE- triathletes to 163 ± 46 ml/s/m2, P < 0.001), but not in LGE + triathletes (169 ± 50ml/s/m2, P = 0.747). CONCLUSION: Despite post-race troponin T release, we did not find detectable myocardial oedema by cardiac magnetic resonance. However, the unfavourable blood pressure response during exercise testing seemed to be associated with post-race cardiac dysfunction, which could explain the occurrence of myocardial fibrosis in triathletes.

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.

Hemostatic abnormalities in adult patients with Marfan syndrome.

BACKGROUND: Aortic root ectasia might induce hemostatic disorders in patients with Marfan syndrome (MFS) via altered blood flow and rheology. The aim of this study was to explore the hemostasis in patients with MFS compared with healthy controls. METHODS: In this cross-sectional case-control study we included patients with verified MFS (n=51) and sex- and age-matched healthy controls (n=50). Main criteria were the aortic root in echocardiography and cardiac magnetic resonance imaging (MRI), and the coagulation status. RESULTS: When compared with healthy controls, patients with MFS showed significantly increased diameters of the aortic roots (43.0±7.72 vs. 28.8±3.74 mm, P<0.001) and aortic Z-scores (4.36±2.77 vs. 0.948±1.09, P<0.001), considerably higher values of Multiplate® tests (e.g., MP-ADP: 878.4±201.7 vs. 660.4±243.6 AU*min, P<0.001) and PFA-100® tests (PFA Col/ADP: 102.5±45.5 vs. 91.1±46.2 s, P<0.05), PTT (30.0±3.91 vs. 28.7±2.50 s, P<0.05) and D-dimers (0.488±0.665 vs. 0.254±0.099 mg/L, P<0.001). In MFS von Willebrand factor (VWF) activity (81.9%±41.8% vs. 106.3%±41.5%, P<0.05) and antigen (93.8%±43.9% vs. 118.8%±47.8%, P<0.05) and factor VIII activity (108.9%±29.6% vs. 126.7%±28.4%, P<0.05) were reduced. Significant positive correlations were found between aortic diameters and D-dimers (all P<0.05), as well as PFA Col/ADP (all P<0.01) in MFS patients. Factor VIII activity correlated significantly negatively with the diameter of the aortic root in MFS (r=-0.55, P<0.05). CONCLUSIONS: In conclusion, our study reveals hemostatic deviations in patients with MFS. Further studies are necessary to understand the causal relationship and the exact pathomechanism.

Brief recommendations for participation in competitive sports of athletes with arterial hypertension: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC).

Owing to its undisputed multitude of beneficial effects, European Society of Cardiology guidelines advocate regular physical activity as a class IA recommendation for the prevention and treatment of cardiovascular disease. Nonetheless, competitive athletes with arterial hypertension may be exposed to an increased risk of cardiovascular events. Guidance to physicians will be given in this summary of our recently published recommendations for participation in competitive sports of athletes with arterial hypertension.

Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks of ET in patients with HFpEF by performing a post hoc analysis of the Ex-DHF-P trial (ISRCTN42524037). Plasma concentrations of 188 endogenous metabolites were measured in 44 ET and 20 usual care (UC) patients at baseline and 3-months follow-up. Metabolic differences between ET and UC from baseline to follow-up were compared and differential responses to ET were examined by random forest feature selection. ET prevented the increase of acetylornithine and carnitine as well as the decrease of three glycerophospholipids. After ET, two opposite metabolic response clusters were identified. Cluster belonging was associated with perceived well-being at baseline and changes in low-density lipoprotein but not with cardiorespiratory, ventilatory or echocardiographic parameters. These two ET-induced metabolic response patterns illustrate the heterogeneity of the HFpEF patient population. Our results suggest that other biological parameters might be helpful besides clinical variables to improve HFpEF patient stratification. Whether this approach improves response prediction regarding ET and other treatments should be explored.

Impact of Myocardial Fibrosis on Left Ventricular Function Evaluated by Feature-Tracking Myocardial Strain Cardiac Magnetic Resonance in Competitive Male Triathletes With Normal Ejection Fraction.

BACKGROUND: To analyze the effect of myocardial fibrosis on left ventricular (LV) function evaluated by feature-tracking strain analysis by cine cardiac magnetic resonance (CMR) in competitive male triathletes with normal ejection fraction (EF).Methods and Results:78 asymptomatic male triathletes with >10 weekly training hours (43±11 years) and 28 male age-matched controls were studied by late gadolinium enhancement (LGE) and cine CMR. Global and segmental radial, longitudinal and circumferential strains were analyzed using feature-tracking cine CMR. Focal non-ischemic LGE was observed in 15 of 78 triathletes (19%, LGE+) with predominance in the basal inferolateral segments. LVEF was normal in LGE+ (62±6%) and LGE- triathletes (62±5%, P=0.958). In contrast, global radial strain was lower in LGE+ triathletes at 40±7% compared with LGE- triathletes (45±7%, P<0.05). Reduced segmental radial strain occurred either in LGE+ segments or in directly adjacent segments. Strain analysis revealed regional differences in controls, with the highest radial and longitudinal strain in the inferolateral segments, which were typically affected by fibrosis in LGE+ triathletes. CONCLUSIONS: Reduced global and regional radial strain suggests a negative effect of myocardial fibrosis on LV function in LGE+ triathletes with normal EF. The observed regional differences in controls with the highest radial and longitudinal strain in the inferolateral segments may explain the typical occurrence of fibrosis in this myocardial region in triathletes.

The early repolarization pattern: Echocardiographic characteristics in elite athletes.

BACKGROUND: The electrocardiographic early repolarization (ER) pattern is associated with idiopathic ventricular fibrillation and increased long-term cardiovascular mortality. Whether structural cardiac aberrations influence the phenotype is unclear. Since ER is particularly common in athletes, we evaluated its prevalence and investigated predisposing echocardiographic characteristics and cardiopulmonary exercise capacity in a cohort of elite athletes. METHODS: A total of 623 elite athletes (age 21 ± 5 years) were examined during annual preparticipation screening from 2006 until 2012 including electrocardiography, echocardiography, and exercise testing. ECGs were analyzed with focus on ER. All athletes participated in a clinical follow-up. RESULTS: The prevalence of ER was 17% (108/623). ER-positive athletes were predominantly male (71%, 77/108), showed a lower heart rate (57.1 ± 9.3 bpm versus 60.0 ± 11.2 bpm; p = 0.015) and a higher lean body mass compared to ER-negative participants (88.1% ± 5.6% versus 86.5% ± 6.3%; p = 0.015). Echocardiographic measurements and cardiopulmonary exercise capacity in male and female athletes with and without ER largely showed similar results. Only the notching ER subtype (n = 15) was associated with an increased left atrial diameter (OR 7.01, 95%CI 1.65-29.83; p = 0.008), a higher left ventricular mass (OR 1.02, 95%CI 1.00-1.03; p = 0.038) and larger relative heart volume (OR 1.01, 95%CI 1.00-1.01; p = 0.01). During a follow-up of 7.4 ± 1.5 years, no severe cardiovascular event occurred in the study sample. CONCLUSIONS: In elite athletes presence of ER is not associated with distinct alterations in echocardiography and cardiopulmonary exercise. Athletes presenting with ER are rather male, lean with a low heart rate.

Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC).

Myocardial diseases are associated with an increased risk of potentially fatal cardiac arrhythmias and sudden cardiac death/cardiac arrest during exercise, including hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, arrhythmogenic cardiomyopathy, and myo-pericarditis. Practicing cardiologists and sport physicians are required to identify high-risk individuals harbouring these cardiac diseases in a timely fashion in the setting of preparticipation screening or medical consultation and provide appropriate advice regarding the participation in competitive sport activities and/or regular exercise programmes. Many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to participate in leisure-time and amateur sport activities to take advantage of the multiple benefits of a physically active lifestyle. In 2005, The European Society of Cardiology (ESC) published recommendations for participation in competitive sport in athletes with cardiomyopathies and myo-pericarditis. One decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of cardiomyopathies and myo-pericarditis. The present document, therefore, aims to offer a comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis and provides pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities.

Recommendations for participation in competitive sports of athletes with arterial hypertension: a position statement from the sports cardiology section of the European Association of Preventive Cardiology (EAPC).

Current guidelines of the European Society of Cardiology advocate regular physical activity as a Class IA recommendation for the prevention and treatment of cardiovascular disease. Despite its undisputed multitude of beneficial effects, competitive athletes with arterial hypertension may be exposed to an increased risk of cardiovascular events. This document is an update of the 2005 recommendations and will give guidance to physicians who have to decide on the risk of an athlete during sport participation.