Exercise-Dependent Modulation of Immunological Response Pathways in Endurance Athletes With and Without Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia characterized by uncoordinated atrial electrical activity. Lone AF occurs in the absence of traditional risk factors and is frequently observed in male endurance athletes, who face a 2- to 5-fold higher risk of AF compared with healthy, moderately active males. Our understanding of how endurance exercise contributes to the pathophysiology of lone AF remains limited. This study aimed to characterize the circulating protein fluctuations during high-intensity exercise as well as explore potential biomarkers of exercise-associated AF. METHODS AND RESULTS: A prospective cohort of 12 male endurance cyclists between the ages of 40 and 65 years, 6 of whom had a history of exercise-associated AF, were recruited to participate using a convenience sampling method. The circulating proteome was subsequently analyzed using multiplex immunoassays and aptamer-based proteomics before, during, and after an acute high-intensity endurance exercise bout to assess temporality and identify potential markers of AF. The endurance exercise bout resulted in significant alterations to proteins involved in immune modulation (eg, growth/differentiation factor 15), skeletal muscle metabolism (eg, α-actinin-2), cell death (eg, histones), and inflammation (eg, interleukin-6). Subjects with AF differed from those without, displaying modulation of proteins previously known to have associations with incident AF (eg, C-reactive protein, insulin-like growth factor-1, and angiopoietin-2), and also with proteins having no previous association (eg, tapasin-related protein and α2-Heremans-Schmid glycoprotein). CONCLUSIONS: These findings provide insights into the proteomic response to acute intense exercise, provide mechanistic insights into the pathophysiology behind AF in athletes, and identify targets for future study and validation.

Atrial fibrillation in middle-aged athletes: Impact on left atrial, ventricular and exercise performance.

High volume endurance training may increase the risk of paroxysmal atrial fibrillation (AF) in middle-aged athletes. Limited data are available describing the cardiovascular phenotype of middle-aged endurance athletes, or the impact of AF on atrial function and exercise performance performed in sinus rhythm. The purpose of this study was to characterize LA phasic function at rest and during exercise in athletes with paroxysmal AF, and to determine its impact on exercise performance. Fifteen endurance trained males (EA) (56 ± 5 years) without AF and 14 endurance trained males with paroxysmal AF (EA-AF) (55 ± 8 years) underwent echocardiography during cycle-ergometry at light and moderate intensities. Resting LA maximal volumes were similar between EA and EA-AF (30 ± 4 vs. 29 ± 8 ml/m2, p = 0.50), and there were no differences in atrial electromechanical delay (AEMD). During moderate intensity exercise, EA-AF had reduced LA conduit (30 ± 6 vs. 40 ± 5 ml/m2, p = 0.002) LA booster volumes (17 ± 5 vs. 21 ± 4 ml/m2, p = 0.021), and reduced LV stroke volumes (100 ± 12 vs. 117 ± 16 ml, p = 0.007). These results demonstrate that exercise testing in athletes with AF unmasks evidence of adverse functional cardiac remodelling that may contribute to impaired exercise performance. It is unclear whether these functional alterations are the consequence of AF. Reductions in LA conduit volume, LA booster volume, and LV stroke volume during exercise may be helpful in clinical management and distinguishing pathologic from physiologic remodelling.

Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

The effect of chronic exercise training and acute exercise on power spectral analysis of heart rate variability.

Moderate to vigorous physical activity performed regularly is cardioprotective and reduces all-cause mortality, concomitant with increased resting heart rate variability (HRV). However, there are contradictory reports regarding the effects of chronic and acute exercise on nocturnal HRV in those performing exercise well-beyond physical activity guidelines. Therefore, the purpose of this study was to compare the power spectral analysis components of HRV in middle-aged endurance athletes (EA) and recreationally active individuals (REC) and explore acute exercise effects in EA. A total of 119 EA (52, 49-57 years) and 32 REC (56, 52-60 years) were recruited to complete 24 h Holter monitoring (GE SEER 1000) in the absence of exercise. Fifty one EA (52, 49-57 years) then underwent 24 h Holter monitoring following an intense bout of endurance exercise. Power spectral HRV analysis was completed hourly and averaged to quantify morning (1000-1200 h), evening (1900-2100 h), and nocturnal (0200-0400 h) HRV. EA had greater very low frequency (VLF) and low frequency (LF) (both p < 0.001) compared to REC. LF/high frequency (HF) was greater in EA at 0200-0400 h (p = 0.04). Among all participants, the change in HR and HF from 1000-1200 to 0200-0400 h was negatively correlated (r = -0.47, p < 0.001). Following acute exercise in EA, only nocturnal HRV was assessed. VLF (p < 0.001) and HF (p = 0.008) decreased, while LF/HF increased (p = 0.02). These results suggest that in EA, both long-term and acute exercises increase nocturnal sympathovagal activity through an increase in LF and decrease in HF, respectively. Further work is required to understand the mechanism underlying reduced nocturnal HRV in middle-aged EA and the long-term health implications.

Long-term outcomes of pulmonary embolism in children and adolescents.

ABSTRACT: Knowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Sex differences in pulmonary and systemic vascular function at rest and during exercise in healthy middle-aged adults.

Our aim was to conduct a sex-disaggregated analysis of pulmonary and systemic vascular function in healthy individuals both at rest and during submaximal exercise. Healthy individuals underwent right-heart catheterization at rest and during submaximal cycling. Hemodynamic data were collected in a control state and with moderate exercise. Pulmonary and systemic vascular variables including: compliance, resistance, and elastance were calculated, indexed to body surface area (BSA), adjusted for age and compared between male and female sex. Thirty-six individuals (18M/18F; 54 ± 7 vs. 58 ± 6 years, p = 0.04) were included. When adjusted for age and indexed to BSA, total pulmonary resistance (TPulmR) (516 ± 73 vs. 424 ± 118 WU m-2, p = 0.03) and pulmonary arterial elastance (PEa) (0.41 ± 0.1 vs. 0.32 ± 0.1 mmHg ml-1 m2, p = 0.03) were higher in females vs. males. Both pulmonary (Cpa) and systemic compliance (Csa) were lower in females vs. males however lost significance with adjustment for age. Systemic arterial elastance (SEa) was higher in females (1.65 ± 0.29 vs. 1.31 ± 0.24 mmHg ml-1, p = 0.05). Secondary analyses demonstrated significant correlations between age and PVR (r = 0.33, p = 0.05), TPulmR (r = 0.35, p = 0.04), Cpa (r = -0.48, p < 0.01), and PEa (r = 0.37, p = 0.03). During exercise, there were greater increases in TPulmR (p = 0.02) and PEa (p = 0.01) in females vs. males. In conclusion, TPulmR and PEa are significantly higher at rest and exercise in females vs. males. Cpa and Csa were lower in females, however this may have been confounded by age. Our results are consistent with the notion that indices of pulmonary and systemic vascular load are higher, related to both older age and female sex, independent of heart failure.

Unraveling the pathophysiology of lower-limb postthrombotic syndrome in adolescents: a proof-of-concept study.

A better understanding of the pathophysiology of pediatric postthrombotic syndrome (PTS) is needed to develop strategies to treat this condition. We investigated calf pump function, exercise capacity, balance in power output, and changes in limb muscle oxygen saturation (SmO2) and fluid content during exercise in 10 pediatric patients with unilateral lower-limb PTS, and in age- and sex-matched controls (1:1-1:2 ratio). Outcomes were investigated using bioimpedance spectroscopy, torque-sensing pedals, and near-infrared spectroscopy during incremental- and constant-load cycling tests. The median age at participation was 17 years (25th-75th percentile, 15-18 years); 68% of participants were females. The median CAPTSure score in the affected leg of affected participants was 35 points (25th-75th percentile, 24-46 points), indicating moderate/severe PTS; 20% of patients had a history of central venous catheter-related thrombosis. Increasing PTS severity was associated with higher calf pump venous volume and higher ejection volume, leading to compensated calf pump performance. We found no evidence of PTS impact on exercise capacity. Leg contribution to power output was similar in affected and unaffected legs. However, the PTS-affected legs showed lower SmO2 during active cycling and recovery with increasing PTS severity, indicating impaired microvascular function in the muscle. These findings suggest that PTS severity is associated with impaired blood flow, presumably from elevated venous pressure during and after exercise. The fact that microvascular function is impaired in young patients with PTS underscores the relevance of developing strategies to mitigate the effects of this chronic vascular disease to minimize its deleterious effects as children grow older.

Alterations of pulmonary vascular afterload in exercise-induced pre- and post-capillary pulmonary hypertension.

Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance-compliance time. In health, afterload stress stabilizes during steady-state exercise. Our objective was to examine alterations of these exercise-associated stresses in states of pre- and post-capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7 min of steady-state exercise at moderate intensity in patients who exhibited Pre-capillary (n = 22) and post-capillary PH (n = 22). Patients with normal exercise hemodynamics (NOR-HD) (n = 32) were also studied. During exercise in all groups, PA wedge pressure increased at 2 min, with no further change at 7 min. In post-capillary PH and NOR-HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7 min of exercise, while in pre-capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance-compliance time at rest (r2  = 0.843) and exercise (r2  = 0.760). Exercise resistance-compliance time was longer in pre-capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance-compliance time was shortest in post-capillary PH compared to pre-capillary PH and NOR-HD and associated with limited increases in exercise diastolic pressure gradient. During steady-state, modest-intensity exercise-specific patterns of pulmonary vascular afterload responses were observed in pre- and post-capillary PH relative to NOR-HD. Longer resistance-compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre-capillary PH, while shorter resistance-compliance time appeared to limit these increases in post-capillary PH.

The role of exercise right heart catheterization to guide pulmonary hypertension therapy in older adults.

The spectrum of patients referred for suspected pulmonary arterial hypertension (PAH) includes a population with clinical features suggestive of pulmonary hypertension due to left heart disease (PH-LHD). Even after right heart catheterization (RHC) performed at rest, it can be a challenge to identify patients who will clearly benefit from PAH drug therapy. Therefore, the objective of this study was to evaluate the role of exercise RHC to influence decisions regarding prescription of PAH drug therapy in this population. A retrospective cohort study was conducted of older adults with risk factors for PH-LHD and suspected PH referred for exercise RHC. One year follow-up was conducted to record clinical outcomes, all changes in PAH drug therapy, and changes in patient-reported quality of life. The final cohort included 61 patients, mean age of 69 ± 10; 44% and 34% had a history of coronary artery disease and atrial fibrillation respectively. Exercise changed the proportional breakdown of hemodynamic diagnoses from 36% No PH, 44% PAH, and 20% PH-LHD at rest to 15% No PH, 36% PAH, and 49% PH-LHD. Although a significant proportion of patients were reclassified as PH-LHD, there was an overall increase in the proportion of patients receiving PAH drug therapy, particularly for those with PAH confirmed by exercise RHC. A total of 11 PAH drug prescriptions were employed before exercise RHC increasing to 24 after (p = 0.002). Patients receiving PAH therapy demonstrated significant improvement in self-reported quality of life. Exercise RHC appeared to influence selection of PAH drug therapy.

Body Habitus Considerations During Right Heart Catheterization.

BACKGROUND: Obese and overweight body habitus are common among patients undergoing right heart catheterization for suspected pulmonary hypertension, but previous studies have described only patients with severe obesity. This study examined the effect of body habitus on intracardiac pressures, thermodilution cardiac output (TDCO), indirect Fick (iFick) cardiac output (CO), and pulmonary vascular resistance (PVR) in subjects with normal cardiopulmonary hemodynamics. METHODS: A retrospective analysis was conducted on healthy volunteers and patients referred for right heart catheterization for dyspnea of unknown origin with normal hemodynamics. Of the 65 subjects (53 ± 14 years; 51% female), 31% were normal weight, 49% were overweight, and 20% had obesity, as defined by a body mass index of 30-39.9 kg/m2. Mixed venous oxygen saturations and intracardiac pressures were compared across body mass index categories. Agreement between iFick CO calculated by 3 formulae, and TDCO and PVR was examined. RESULTS: No differences in intracardiac pressures were observed, but mixed venous oxygen saturations were lower in the obese group. iFick CO underestimated TDCO, particularly with the LaFarge formula, with a systematic difference of 0.33 L/min for every 1 L/min increase in CO. This difference was largest in the obese group-on average by 23% ± 10%, translating to an overestimation of PVR by 34% ± 16% on average. CONCLUSIONS: In individuals without severe obesity, intracardiac pressures are not different, but mixed venous oxygen saturations are lower. Obesity confounds estimations of CO and PVR by iFick methods, which could result in inappropriate hemodynamic classification. These data can inform best practices in hemodynamic assessment of populations with obesity.

INTRODUCTION: Les habitus corporels liés à l'obésité et à l'embonpoint sont fréquents chez les patients qui subissent un cathétérisme du cœur droit en raison d'une suspicion d'hypertension pulmonaire, mais les études antérieures n'ont porté que sur les patients atteints d'une obésité sérieuse. La présente étude portait sur les répercussions des habitus corporels sur les pressions intracardiaques, le débit cardiaque obtenu par thermodilution (DCTD), le débit cardiaque (DC) calculé selon le principe indirect de Fick (iFick) et la résistance vasculaire pulmonaire (RVP) chez les sujets ayant une hémodynamie cardiopulmonaire normale. MÉTHODES: Nous avons mené une analyse rétrospective auprès de volontaires en bonne santé et de patients orientés pour un cathétérisme cardiaque droit en raison de dyspnée d'origine inconnue, mais qui avaient une hémodynamie normale. Au sein de 65 sujets (53 ± 14 ans; 51 % de femmes), 31 % avaient un poids normal, 49 % faisaient de l'embonpoint et 20 % souffraient d'obésité d'après l'indice de masse corporelle entre 30-39,9 kg/m2. Nous avons comparé les saturations veineuses mixtes en oxygène et les pressions intracardiaques de toutes les catégories d'indice de masse corporelle. Nous avons examiné la concordance entre le calcul du DC selon le principe iFick au moyen de 3 formules, ainsi que le DCTD et la RVP. RÉSULTATS: Les pressions intracardiaques n'ont montré aucune différence, mais les saturations veineuses mixtes en oxygène étaient plus faibles chez les sujets obèses. Le DC calculé selon le principe iFick a démontré une sous-estimation du DCTD, particulièrement lors du calcul au moyen de la formule LaFarge, qui a révélé une différence systématique de 0,33 L/min à chaque augmentation du DC de 1 L/min. Cette différence qui était plus importante chez les sujets obèses (en moyenne de 23 % ± 10 %, se traduisait en moyenne par une surestimation de la RVP de 34 % ± 16 %). CONCLUSIONS: Chez les individus non atteints d'une obésité sérieuse, les pressions intracardiaques ne sont pas différentes, mais les saturations veineuses mixtes en oxygène sont plus faibles. L'obésité fait remettre en cause les estimations du DC et de la RVP par les méthodes iFick, lesquelles pourraient donner lieu à une classification hémodynamique erronée. Ces données peuvent permettre d'établir des pratiques exemplaires lors de l'évaluation hémodynamique des populations atteintes d'obésité.

Atrial structure and function in middle-aged, physically-active males and females: A cardiac magnetic resonance study.

Recent studies have reported on an association between endurance sport, atrial enlargement and the development of lone atrial fibrillation in younger, male cohorts. The atrial morphology and function of middle-aged, physically-active males and females have not been well studied. We hypothesized that middle-aged males would demonstrate larger left atrium (LA) and right atrium (RA) volumes compared to females, but atrial function would not differ. LA and RA volume and function were evaluated at rest in healthy adults, using a standardized 3.0Tesla cardiac magnetic resonance protocol. Physical activity, medical history, and maximal oxygen consumption ( V ˙ O 2 peak ) were also assessed. Physically-active, middle-aged men (n = 60; 54 ± 5 years old) and women (n = 30; 54 ± 5 years old) completed this study. Males had a higher body mass index, systolic blood pressure, and V ˙ O 2 peak than females (p < .05 for all), despite similar reported physical activity levels. Absolute and BSA and height-indexed LA and RA maximum volumes were higher in males relative to females, despite no differences in ejection fractions (p < .05 for all). In multivariable regression, male sex p < .001) and V ˙ O 2 peak (p = .004) were predictors of LA volume (model R2  = 0.252), whereas V ˙ O 2 peak (p < .001), male sex (p = .03), and RV EF (p < .05) were predictors of RA volume (model R2  = 0.377). While middle-aged males exhibited larger atrial volumes relative to females, larger, prospective studies are needed to explore the magnitude of physiologic atrial remodeling and functional adaptations in relation to phenotypic factors.

Drugs in phase I and II clinical development for the prevention of stroke in patients with atrial fibrillation.

INTRODUCTION: Atrial fibrillation is the most frequently diagnosed cardiac arrhythmia globally and is associated with ischemic stroke and heart failure. Patients with atrial fibrillation are typically prescribed long-term anticoagulants in the form of either vitamin K antagonists or non-vitamin K antagonist oral anticoagulants; however, both carry a potential risk of adverse bleeding. AREAS COVERED: This paper sheds light on emerging anticoagulant agents which target clotting factors XI and XII, or their activated forms - XIa and XIIa, respectively, within the intrinsic coagulation pathway. The authors examined data available on PubMed, Scopus, and the clinical trials registry of the United States National Library of Medicine (www.clinicaltrials.gov). EXPERT OPINION: Therapies targeting factors XI or XII can yield anticoagulant efficacy with the potential to reduce adverse bleeding. Advantages for targeting factor XI or XII include a wider therapeutic window and reduced bleeding. Long-term follow-up studies and a greater understanding of the safety and efficacy are required. Atrial fibrillation is a chronic disease and therefore the development of oral formulations is key.

A Novel Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Biomarker-Anti-DSG2-Is Absent in Athletes With Right Ventricular Enlargement.

BACKGROUND: Right ventricular (RV) enlargement is common in endurance athletes. It is usually considered to be physiological, but it is possible that this remodelling is adverse, manifesting as a variant of arrhythmogenic right ventricular cardiomyopathy (ARVC), termed "exercise-induced ARVC." A novel biomarker (anti-desmoglein-2 [anti-DSG2] antibody) has been shown to indicate ARVC with high sensitivity and specificity and may be an immune response to breakdown of RV desmosomes. It is not known if this antibody is present in endurance athletes with RV enlargement but without clinical ARVC. METHODS: Middle-aged, healthy endurance athletes with RV enlargement on cardiac magnetic resonance imaging had serum tested for the presence of the anti-DSG2 antibody. All athletes also underwent Holter monitoring, a signal-averaged electrocardiogram, and an exercise questionnaire. RESULTS: A total of 30 athletes (20 men, 10 women, average age 53 ± 6 years) were enrolled in this study with median RV end-diastolic volume indexes of 117.1 mL/m2 (men) and 103.5 mL/m2 (women). Athletes demonstrated other characteristics of endurance training, including depolarization abnormalities (abnormal signal-averaged electrocardiogram, 19 of 30) and incomplete right bundle branch block (8 of 30). No athlete met criteria for definite or probable ARVC. None of the athletes tested positive for anti-DSG2 antibody. CONCLUSIONS: Among middle-aged endurance athletes with RV enlargement, the anti-DSG2 antibody, a suggested ARVC biomarker, is absent in all and is highly specific in this cohort (95% confidence interval, 88%-100%). Despite significant RV remodelling, these athletes did not express a previously characterized pathologic biomarker known to be sensitive for ARVC. Physiological exercise remodelling and pathologic ARVC remodelling are likely separate processes.

INTRODUCTION: L'augmentation du volume du ventricule droit (VD) est fréquente chez les sportifs d'endurance. On considère habituellement que ce remodelage est physiologique, mais il est possible qu'il soit indésirable, c'est-à-dire qu'il révèle une variante de la cardiomyopathie arythmogène du ventricule droit (CAVD), appelée « CAVD induite par l'exercice ¼. Il a été démontré qu'un nouveau biomarqueur (l'anticorps anti-desmogléine 2 [anti-DSG2]) présente une sensibilité et une spécificité élevées pour dépister la CAVD et qu'il peut être une réponse immunitaire à la dégradation des desmosomes du VD. On ne sait pas si cet anticorps est présent chez les sportifs d'endurance qui ont une augmentation du volume du VD, sans CAVD clinique. MÉTHODES: Les sportifs d'endurance d'âge moyen en bonne santé qui ont une augmentation du volume du VD à l'imagerie cardiaque par résonance magnétique ont subi une épreuve pour vérifier la présence de l'anticorps anti-DSG2 dans le sérum. Tous les athlètes ont également eu une surveillance par la méthode de Holter, un électrocardiogramme à signaux moyennés et un questionnaire sur l'exercice. RÉSULTATS: Nous avons inscrit à cette étude un total de 30 athlètes (20 hommes, 10 femmes, âge moyen de 53 ± 6 ans) dont les indices volumiques télédiastoliques médians du VD des hommes étaient de 117,1 ml/m2 et des femmes, de 103,5 ml/m2. Les athlètes ont démontré d'autres caractéristiques de l'entraînement en endurance, notamment des anomalies de la dépolarisation (électrocardiogramme à signaux moyennés anormal, 19 sur 30) et un bloc de branche droit incomplet (8 sur 30). Aucun athlète n'a répondu aux critères de CAVD définie ou probable. Aucun des athlètes n'a eu de résultats positifs au test de dépistage des anticorps anti-DSG2. CONCLUSIONS: Chez tous les sportifs d'endurance d'âge moyen qui ont une augmentation du volume du VD, l'anticorps anti-DSG2, un biomarqueur proposé pour dépister la CAVD, est absent et est hautement spécifique dans cette cohorte (intervalle de confiance à 95 %, 88 %-100 %). En dépit d'un remodelage important du VD, les athlètes n'ont pas exprimé le biomarqueur pathologique, auparavant caractérisé, connu pour être sensible au dépistage de la CAVD. Le remodelage physiologique induit par l'exercice et le remodelage pathologique associé à la CAVD sont des processus probablement distincts.

Normal and Abnormal Relationships of Pulmonary Artery to Wedge Pressure During Exercise.

Background Resting right heart catheterization can assess both left heart filling and pulmonary artery (PA) pressures to identify and classify pulmonary hypertension. Although exercise may further elucidate hemodynamic abnormalities, current pulmonary hypertension classifications do not consider the expected interrelationship between PA and left heart filling pressures. This study explored the utility of this relationship to enhance the classification of exercise hemodynamic phenotypes in pulmonary hypertension. Methods and Results Data from 36 healthy individuals (55, 50-60 years, 50% male) and 85 consecutive patients (60, 49-71 years, 48% male) with dyspnea and/or suspected pulmonary hypertension of uncertain etiology were analyzed. Right heart catheterization was performed at rest and during semiupright submaximal cycling. To classify exercise phenotypes in patients, upper 95% CIs were identified from the healthy individuals for the change from rest to exercise in mean PA pressure over cardiac output (ΔmPAP/ΔCO ≤3.2 Wood units [WU]), pulmonary artery wedge pressure over CO (ΔPAWP/ΔCO ≤2 mm Hg/L per minute), and exercise PA pulse pressure over PAWP (PP/PAWP ≤2.5). Among patients with a ΔmPAP/ΔCO ≤3.2 WU, the majority (84%) demonstrated a ΔPAWP/ΔCO ≤2 mm Hg/L per minute, yet 23% demonstrated an exercise PP/PAWP >2.5. Among patients with a ΔmPAP/ΔCO >3.2 WU, 37% had an exercise PP/PAWP >2.5 split between ΔPAWP/ΔCO groups. Patients with normal hemodynamic classification declined from 52% at rest to 36% with exercise. Conclusions The addition of PP/PAWP to classify exercise hemodynamics uncovers previously unrecognized abnormal phenotypes within each ΔmPAP/ΔCO group. Our study refines abnormal exercise hemodynamic phenotypes based on an understanding of the interrelationship between PA and left heart filling pressures.

Left Ventricular Fibrosis in Middle-Age Athletes and Physically Active Adults.

INTRODUCTION: Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and T1 mapping techniques enable the quantification of focal and diffuse myocardial LGE, respectively. Studies have shown evidence of fibrosis in middle-age athletes, but not relative to physically active (PA) adults who perform recommended physical activity levels. Therefore, we examined cardiac remodeling and presence of left ventricular (LV) LGE and T1 values in both recreational middle-age endurance athletes (EA) and PA adults. METHODS: Healthy EA and PA adults (45-65 yr) completed a standardized 3-T CMR protocol with ventricular volumetry, LV LGE, and T1 mapping. RESULTS: Seventy-two EA and 20 PA participants (mean age, 53 ± 5 vs 56 ± 4 yr; P < 0.01; V˙O2peak = 50 ± 7 vs 37 ± 9 mL·kg·min, P < 0.0001) were examined, with CMR data available in 89/92 participants. Focal LV LGE was observed in 30% of participants (n = 27/89): 33% of EA (n = 23/69; 33%) and 20% of PA (n = 4/20; 20%). LGE was present at the right ventricular hinge point (n = 21/89; 23.5%) or identified as ischemic (n = 2/89; 2%) or nonischemic (n = 4/89; 4%). Focal LV LGE was observed similarly in both EA and PA (P = 0.25). EA had larger LV chamber sizes and T1 native values (1169 ± 35 vs 1190 ± 26, P = 0.02) compared with PA, with similar LV ejection fraction. Global extracellular volume (ECV) was similar in both EA and PA (22.6% ± 3.5% vs 21.5% ± 2.6%, P = 0.26), with no relationship between global ECV and LV mass (r = -0.16, P = 0.19). CONCLUSIONS: Focal LGE at the right ventricular hinge point was detected at the same frequency in both groups, was unrelated to demographic or clinical indices, and was found without evidence of global ECV expansion in EA, suggesting a physiologic remodeling response. The long-term clinical implications of hinge-point LGE require clarification using prospective, long-term follow-up studies.

Heart rate variability and recovery following maximal exercise in endurance athletes and physically active individuals.

The purpose of this study was to determine potential adverse cardiac effects of chronic endurance training by comparing sympathovagal modulation via heart rate variability (HRV) and heart rate recovery (HRR) in middle-aged endurance athletes (EA) and physically active individuals (PA) following maximal exercise. Thirty-six (age, 53 ± 5 years) EA and 19 (age, 56 ± 5 years) PA were recruited to complete a 2-week exercise diary and graded exercise to exhaustion. Time domain and power spectral HRV analyses were completed on recorded R-R intervals. EA had a greater HRR slope following exercise (95% confidence interval, 0.0134-0.0138 vs. 0.0101-0.0104 beats/s; p < 0.001). While EA had greater HRR at 1-5 min after exercise (all p < 0.01), PA and EA did not differ when expressed as a percentage of baseline heart rate (130 ± 19 vs. 139 ± 19; p = 0.2). Root mean square of successive differences in R-R intervals (rest and immediately after exercise) were elevated in EA (p < 0.05). Low-frequency (LF) and high-frequency (HF) spectral components were nonsignificantly elevated after exercise (p = 0.045-0.147) in EA while LF/HF was not different (p = 0.529-0.986). This data suggests greater HRR in EA may arise in part due to a lower resting HR. While nonsignificant elevations in HF and LF in EA produces a LF/HF similar to PA, absolute spectral component modulation differed. These observations require further exploration. Novelty Acute effects of exercise on HRV in EA compared with a relevant control group, PA, are unknown. EA had greater HRR and nonsignificant elevations in LF and HF compared with PA, yet LF/HF was not different. Future work should explore the implications of this observation.

Exercise Right Heart Catheterisation in Cardiovascular Diseases: A Guide to Interpretation and Considerations in the Management of Valvular Heart Disease.

The use of exercise right heart catheterisation for the assessment of cardiovascular diseases has regained attention recently. Understanding physiologic haemodynamic exercise responses is key for the identification of abnormal haemodynamic patterns. Exercise total pulmonary resistance >3 Wood units identifies a deranged haemodynamic response and when total pulmonary resistance exceeds 3 Wood units, an exercise pulmonary artery wedge pressures/cardiac output slope >2 mmHg/l/min indicates the presence of underlying exercise-induced pulmonary hypertension related to left heart disease. In the evolving field of transcatheter interventions for valvular heart disease, exercise right heart catheterisation may objectively unmask symptoms and underlying haemodynamic abnormalities. Further studies are needed on the use of the procedure to inform the selection of patients who might receive the most benefit from transcatheter interventions for valvular heart diseases.