Differential response to preoperative exercise training in patients candidates to cardiac valve replacement.

BACKGROUND: There is lack of evidence regarding safety, effectiveness and applicability of prehabilitation on cardiac surgery population, particularly in patients candidates to cardiac valve replacement. The aim of the study is to assess and compare the effect of a multimodal prehabilitation program on functional capacity in patients with severe aortic stenosis (AoS) and severe mitral regurgitation (MR) proposed for valve replacement surgery. METHODS: Secondary analysis from a randomised controlled trial whose main objective was to analyze the efficacy of a 4-6 weeks multimodal prehabilitation program in cardiac surgery on reducing postoperative complications. For this secondary analysis, only candidates for valve replacement surgery were selected. The primary outcome was the change in endurance time (ET) from baseline to preoperative assessment measured by a cycling constant work-rate cardiopulmonary exercise test. RESULTS: 68 patients were included in this secondary analysis, 34 (20 AoS and 14 MR) were allocated to the prehabilitation group and 34 (20 AoS and 14 MR) to control group. At baseline, patients with AoS had better left systolic ventricular function and lower prevalence of atrial fibrillation compared to MR (p = 0.022 and p = 0.035 respectively). After prehabilitation program, patients with MR showed greater improvement in ET than AoS patients (101% vs. 66% increase from baseline). No adverse events related to the prehabilitation program were observed. CONCLUSIONS: A 4-6 week exercise training program is safe and overall improves functional capacity in patients with severe AoS and MR. However, exercise response is different according to the cardiac valve type disfunction, and further studies are needed to know the factors that predispose some patients to have better training response. TRIAL REGISTRATION: The study has been registered on the Registry of National Institutes of Health ClinicalTrials.gov (NCT03466606) (05/03/2018).

Sport PRactice and its Effects on aortic size and valve function in bicuspid Aortic valve Disease: a cross-sectional report from the SPREAD study.

OBJECTIVE: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV). METHODS: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV. We assessed valve function, aortic size and biventricular measures using echocardiography. Individuals with established moderate-severe AV stenosis, regurgitation or significant aortic dilation were excluded from the study. RESULTS: The study population comprised 504 participants: 186 competitive athletes with BAV (84% males; age 30±11 years), 193 competitive athletes with TAV and 125 non-athletes with BAV. The aortic annulus was greater in athletes with BAV than athletes with TAV and non-athletes with BAV (p<0.001). Both athletic and non-athletic individuals with BAV had greater sinuses of Valsalva, sino-tubular junction and ascending aorta diameters than athletes with TAV (p<0.001). However, no significant differences were found between athletes and non-athletes with BAV. Left ventricular index volumes and mass were greater in athletes with BAV than in the other two groups (p<0.001). Individuals with BAV (athletes and non-athletes) had greater mean gradients than TAV athletes. CONCLUSION: This multicentre international study demonstrates no differences between athletes with BAV and non-athletes with BAV regarding aortic valve function or aortic dimensions. However, athletes with BAV have larger aortic diameters and a relatively worse valvular function than athletes with TAV.

Sex as a main determinant of bi-atrial acute and chronic adaptation to exercise.

PURPOSE: Athlete's heart encompasses multiple physiological cardiac adaptations, although less is known at atrial level. How sex may influence the type and extent of atrial adaptations to exercise stimuli is also unknown. Our objective was to compare gender differences of echocardiographic atrial function indices in response to exercise in endurance athletes (EAs). METHODS: Highly trained (> 10 h/week) endurance athletes performed a maximal cardiopulmonary exercise test (CPET). Echocardiographic evaluation was performed at rest and immediately after exercise. Atria analysis consisted of standard and speckle-tracking echocardiographic assessment of atrial dimensions and contractile, reservoir, and conduit functions with myocardial deformation. RESULTS: 80 EAs (55% women) were enrolled and performed excellent CPET (129.6% of predicted VO2 maximal consumption). At rest, left atrial (LA) volumes and strain were similar between men and women. Women had lower right atrial (RA) volumes (26.7 vs 32.9 ml/m2, p < 0.001) and higher reservoir and conduit strain absolute values. After exercise, women exhibited a larger improvement in reservoir and conduit LA strain, and the same trend was observed for the RA. In EAs with LA dilatation on baseline (~ 50%), women persistently showed higher increase in reservoir and conduit strain profile with exercise compared to men. CONCLUSION: In highly trained EAs, women have similar or even lower atrial dimensions remodelling compared to men, but better function based on reservoir and conduit strain values both at rest and in response to exercise. This phenomenon should be confirmed in larger studies and its potential role in the development of supraventricular arrhythmias, addressed in a specifically designed protocol.

Assessment of myocardial deformation with CMR: a comparison with ultrasound speckle tracking.

OBJECTIVES: Myocardial deformation integrated with cardiac dimensions provides a comprehensive assessment of cardiac function, which has proven useful to differentiate cardiac pathology from physiological adaptation to situations such as chronic intensive training. Feature tracking (FT) can measure myocardial deformation from cardiac magnetic resonance (CMR) cine sequences; however, its accuracy is not yet fully validated. Our aim was to compare the accuracy and reproducibility of FT with speckle tracking echocardiography (STE) in highly trained endurance athletes. METHODS: Ninety-three endurance athletes (> 12-h training/week during the last 5 years, 52% male, 35 ± 5.1 years old) and 72 age-matched controls underwent resting CMR and transthoracic echocardiography to assess biventricular exercise-induced remodeling and biventricular global longitudinal strain (GLS) by CMR-FT and STE. RESULTS: Strain values were significantly lower when assessed by CMR-FT compared to STE (p < 0.001), with good reproducibility for the left ventricle (bias = 3.94%, limit of agreement [LOA] = ± 4.27 %) but wider variability for right ventricle strain. Strain values by both techniques proportionally decreased with increasing ventricular volumes, potentially depicting the functional biventricular reserve that characterizes athletes' hearts. CONCLUSIONS: Biventricular longitudinal strain values were lower when assessed by FT as compared to STE. Both methods were statistically comparable when measuring LV strain but not RV strain. These differences might be justified by the lower in-plane spatial and temporal resolution of FT, which is particularly relevant for the complex anatomy of the RV. KEY POINTS: • Strain values were significantly lower when assessed by FT as compared to STE, which was expected due to the lower in-plane spatial and temporal resolution of FT versus STE. • Both methods were statistically comparable when measuring LV strain but not for RV strain analysis. • Characterizing the normal ranges and reproducibility of strain metrics by FT is an important step toward its clinical applicability, since it can be assessed offline and applied to routinely acquired cine CMR images.

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part 2: ventricular arrhythmias, channelopathies, and implantable defibrillators.

This paper belongs to a series of recommendation documents for participation in leisure-time physical activity and competitive sports by the European Association of Preventive Cardiology (EAPC). Together with an accompanying paper on supraventricular arrhythmias, this second text deals specifically with those participants in whom some form of ventricular rhythm disorder is documented, who are diagnosed with an inherited arrhythmogenic condition, and/or who have an implanted pacemaker or cardioverter defibrillator. A companion text on recommendations in athletes with supraventricular arrhythmias is published in the European Journal of Preventive Cardiology. Since both texts focus on arrhythmias, they are the result of a collaboration between EAPC and the European Heart Rhythm Association (EHRA). The documents provide a framework for evaluating eligibility to perform sports, based on three elements, i.e. the prognostic risk of the arrhythmias when performing sports, the symptomatic impact of arrhythmias while performing sports, and the potential progression of underlying structural problems as the result of sports.

Recommendations for participation in competitive sport in adolescent and adult athletes with Congenital Heart Disease (CHD): position statement of the Sports Cardiology & Exercise Section of the European Association of Preventive Cardiology (EAPC), the European Society of Cardiology (ESC) Working Group on Adult Congenital Heart Disease and the Sports Cardiology, Physical Activity and Prevention Working Group of the Association for European Paediatric and Congenital Cardiology (AEPC).

Improved clinical care has led to an increase in the number of adults with congenital heart disease (CHD) engaging in leisure time and competitive sports activities. Although the benefits of exercise in patients with CHD are well established, there is a low but appreciable risk of exercise-related complications. Published exercise recommendations for individuals with CHD are predominantly centred on anatomic lesions, hampering an individualized approach to exercise advice in this heterogeneous population. This document presents an update of the recommendations for competitive sports participation in athletes with cardiovascular disease published by the Sports Cardiology & Exercise section of the European Association of Preventive Cardiology (EAPC) in 2005. It introduces an approach which is based on the assessment of haemodynamic, electrophysiological and functional parameters, rather than anatomic lesions. The recommendations provide a comprehensive assessment algorithm which allows for patient-specific assessment and risk stratification of athletes with CHD who wish to participate in competitive sports.

Molecular disturbance underlies to arrhythmogenic cardiomyopathy induced by transgene content, age and exercise in a truncated PKP2 mouse model.

Arrhythmogenic cardiomyopathy (ACM) is a disorder characterized by a progressive ventricular myocardial replacement by fat and fibrosis, which lead to ventricular arrhythmias and sudden cardiac death. Mutations in the desmosomal gene Plakophilin-2 (PKP2) accounts for >40% of all known mutations, generally causing a truncated protein. In a PKP2-truncated mouse model, we hypothesize that content of transgene, endurance training and aging will be determinant in disease progression. In addition, we investigated the molecular defects associated with the phenotype in this model. We developed a transgenic mouse model containing a truncated PKP2 (PKP2-Ser329) and generated three transgenic lines expressing increasing transgene content. The pathophysiological features of ACM in this model were assessed. While we did not observe fibro-fatty replacement, ultrastructural defects were exhibited. Moreover, we observed transgene content-dependent development of structural (ventricle dilatation and dysfunction) and electrophysiological anomalies in mice (PR interval and QRS prolongation and arrhythmia induction). In concordance with pathological defects, we detected a content reduction and remodeling of the structural proteins Desmocollin-2, Plakoglobin, native Plakophilin-2, Desmin and ß-Catenin as well as the electrical coupling proteins Connexin 43 and cardiac sodium channel (Nav1.5). Surprisingly, we observed structural but not electrophysiological abnormalities only in trained and old mice. We demonstrated that truncated PKP2 provokes ACM in the absence of fibro-fatty replacement in the mouse. Transgene dose is essential to reveal the pathology, whereas aging and endurance training trigger limited phenotype. Molecular abnormalities underlay the structural and electrophysiological defects.

Cardiopulmonary, biomarkers, and vascular responses to acute hypoxia following cardiac transplantation.

Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty-six CTx recipients and 17 age-matched healthy controls (HC) were recruited. Sixteen (16) patients (42%) had cardiac allograft vasculopathy (CAV). Cardiopulmonary responses to maximal and submaximal exercise at 21% O2 , 20-minutes hypoxia (11.5% O2 ), and following a 10-minute exposure to 11.5% O2 using 30% of peak power output were completed. Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), suppression of tumorigenicity 2 (ST2) were measured at baseline and at peak stress. Endothelial peripheral function was assessed using near-infrared spectroscopy. Compared with HC, CTx presented a lesser O2 desaturation both at rest (-19.4 ± 6.8 [CTx] vs -24.2 ± 6.0% O2 [HC], P < 0.05) and following exercise (-23.2 ± 4.9 [CTx] vs -26.2 ± 4.7% O2 [HC], P < 0.05). CTx patients exhibited a significant decrease in peak oxygen uptake. IL-6 and VEGF levels were significantly higher in CTx recipients in basal conditions but did not change in response to acute stress. CTx patients exhibit a favorable ventilatory and overall response to hypoxic stress. These data provide further insights on the good adaptability of CTx to exposure to high altitude.

Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s-1, SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s-1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s-1, MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive.NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function.

Influence of gender on right ventricle adaptation to endurance exercise: an ultrasound two-dimensional speckle-tracking stress study.

BACKGROUND: Characteristic right ventricle (RV) remodelling is related to endurance exercise in male athletes (MAs), but data in female athletes (FAs) are scarce. Our aim was to evaluate sex-related influence on exercise-induced RV remodelling and on RV performance during exercise. METHODS: Forty endurance athletes (>10 training hours/week, 50% female) and 40 age-matched controls (<3 h moderate exercise/week, 50% female) were included. Echocardiography was performed at rest and at maximum cycle-ergometer effort. Both ventricles were analysed by standard and speckle-tracking echocardiography. RESULTS: Endurance training induced similar structural and functional cardiac remodelling in MAs and FAs, characterized by bi-ventricular dilatation [~34%, left ventricle (LV); 29%, RV] and normal bi-ventricular function. However, males had larger RV size (p < 0.01), compared to females: RV end-diastolic area (cm2/m2): 15.6 ± 2.2 vs 11.6 ± 1.7 in athletes; 12.2 ± 2.7 vs 8.6 ± 1.6 in controls, respectively, and lower bi-ventricular deformation (RV global longitudinal strain (GLS) (%): -24.0 ± 3.6 vs -29.2 ± 3.1 in athletes; -24.9 ± 2.5 vs -30.0 ± 1.9 in controls, and LVGLS: -17.5 ± 1.4 vs -21.9 ± 1.9 in athletes; -18.7 ± 1.2 vs -22.5 ± 1.5 in controls, respectively, p < 0.01). During exercise, the increase in LV function was positively correlated (p < 0.01) with increased cardiac output (∆%LV ejection fraction, r = +0.46 and ∆%LVGLS, r = +0.36). Improvement in RV performance was blunted at high workloads, especially in MAs. CONCLUSION: Long-term endurance training induced similar bi-ventricular remodelling in MAs and FAs. Independently of training load, males had larger RV size and lower bi-ventricular deformation. Improvement in RV performance during exercise was blunted at high workloads, especially in MAs. The potential mechanisms underlying these findings warrant further investigation.