Large individual differences exist in aerobic fitness in childhood and adolescence, but the relative contribution of genetic factors to this variation remains to be established. In a sample of adolescent twins and siblings (n = 479), heart rate (HR) and maximal oxygen uptake (V̇o2max) were recorded during the climax of a graded maximal exercise test. In addition, V̇o2max was predicted in two graded submaximal exercise tests on the cycle ergometer and the treadmill, using extrapolation of the HR/V̇o2 curve to the predicted HRmax. Heritability estimates for measured V̇o2max were 60% in ml/min and 55% for V̇o2max in ml·min(-1)·kg(-1). Phenotypic correlations between measured V̇o2max and predicted V̇o2max from either submaximal treadmill or cycle ergometer tests were modest (0.57 < r < 0.70), in part because of the poor agreement between predicted and actual HRmax. The majority of this correlation was explained by genetic factors; therefore, the submaximal exercise tests still led to very comparable estimates of heritability of V̇o2max. To arrive at a robust estimate for the heritability of V̇o2max in children to young adults, a sample size weighted meta-analysis was performed on all extant twin and sibling studies in this age range. Eight studies, including the current study, were meta-analyzed and resulted in a weighted heritability estimate of 59% (ml/min) and 72% (ml·min(-1)·kg(-1)) for V̇o2max. Taken together, the twin-sibling study and meta-analyses showed that from childhood to early adulthood genetic factors determine more than half of the individual differences in V̇o2max.

Background-Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (RYR2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying a RYR2 mutation is limited. Methods and Results-One-hundred sixteen relatives carrying a RYR2 mutation from 15 families who were identified by cascade screening of the RYR2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a RYR2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5-11.5; P=0.007, compared with N-terminal domain). Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3-19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4-20.9 years). Conclusions-Relatives carrying an RYR2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low. (Circ Arrhythm Electrophysiol. 2012;5:748-756.)

Rationale Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia. Objective To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. Methods and Results Using CPVT mouse models (Casq2−/− and RyR2R4496C+/− mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia (VT) in 86% of Casq2−/− mice (6/7) and significantly reduced the ventricular arrhythmia (VA) score (atropine: 0.6±0.2 vs. vehicle: 1.7±0.3, p<0.05). Atrial overdrive pacing completely prevented VA in 16/19 (84%) Casq2−/− and in 7/8 (88%) RyR2R4496C+/− mice and significantly reduced ventricular premature beats in both CPVT models (p<0.05). Rapid pacing also prevented spontaneous calcium waves and triggered beats in isolated CPVT myocytes. In humans, heart-rate dependence of CPVT was evaluated by screening a CPVT patient registry for antiarrhythmic drug-naïve individuals that reached >85% of their maximum predicted heart rate during exercise testing. All 18 CPVT patients who fulfilled the inclusion criteria exhibited VA before reaching 87% of maximum heart rate. In six CPVT patients (33%), VA were paradoxically suppressed as sinus heart rates increased further with continued exercise. Conclusions Accelerated supraventricular rates suppress VAs in two CPVT mouse models and in a subset of CPVT patients. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced VT in treatment-refractory CPVT patients.

Physical fitness can be defined as a set of components that determine exercise ability and influence performance in sports. This study investigates the genetic and environmental influences on individual differences in explosive leg strength (vertical jump), handgrip strength, balance, and flexibility (sit-and-reach) in 227 healthy monozygotic and dizygotic twin pairs and 38 of their singleton siblings (mean age 17.2 ± 1.2). Heritability estimates were 49 % (95 % CI 35–60 %) for vertical jump, 59 % (95 % CI 46–69 %) for handgrip strength, 38 % (95 % CI 22–52 %) for balance, and 77 % (95 % CI 69–83 %) for flexibility. In addition, a meta-analysis was performed on all twin studies in children, adolescents and young adults reporting heritability estimates for these phenotypes. Fifteen studies, including results from our own study, were meta-analyzed by computing the weighted average heritability. This showed that genetic factors explained most of the variance in vertical jump (62 %; 95 % CI 47–77 %, N = 874), handgrip strength (63 %; 95 % CI 47–73 %, N = 4516) and flexibility (50 %; 95 % CI 38–61 %, N = 1130) in children and young adults. For balance this was 35 % (95 % CI 19–51 %, N = 978). Finally, multivariate modeling showed that the phenotypic correlations between the phenotypes in current study (0.07 < r < 0.27) were mostly driven by genetic factors. It is concluded that genetic factors contribute significantly to the variance in muscle strength, flexibility and balance; factors that may play a key role in the individual differences in adolescent exercise ability and sports performance.

Background Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood. The main aim was to determine the maturation of different cardiac sympathetic‐(SNS) and parasympathetic nervous system (PNS) activity parameters in healthy patients aged 0.5 to 20 years. A second aim was to determine potential sex differences. Methods and Results Five studies covering the 0.5‐ to 20‐year age range provided impedance‐ and electrocardiography recordings from which heart rate, different PNS‐parameters (eg, respiratory sinus arrhythmia) and an SNS‐parameter (pre‐ejection period) were collected. Age trends were computed in the mean values across 12 age‐bins and in the age‐specific variances. Age was associated with changes in mean and variance of all parameters. PNS‐activity followed a cubic trend, with an exponential increase from infancy, a plateau phase during middle childhood, followed by a decrease to adolescence. SNS‐activity showed a more linear trend, with a gradual decrease from infancy to adolescence. Boys had higher SNS‐activity at ages 11 to 15 years, while PNS‐activity was higher at 5 and 11 to 12 years with the plateau level reached earlier in girls. Interindividual variation was high at all ages. Variance was reasonably stable for SNS‐ and the log‐transformed PNS‐parameters. Conclusions Cardiac PNS‐ and SNS‐activity in childhood follows different maturational trajectories. Whereas PNS‐activity shows a cubic trend with a plateau phase during middle childhood, SNS‐activity shows a linear decrease from 0.5 to 20 years. Despite the large samples used, clinical use of the sex‐specific centile and percentile normative values is modest in view of the large individual differences, even within narrow age bands.

Objectives Individual differences in adolescent exercise behavior are strongly influenced by genetic factors. The affective response to exercise is a potential source of these genetic influences. To test its role in the motivation to exercise, we estimated the heritability of the affective responses during and after exercise and the overlap with the genetic factors influencing regular voluntary exercise behavior. Design 226 twin pairs and 38 siblings completed two submaximal exercise tests on a cycle ergometer and a treadmill and a maximal exercise test on a cycle ergometer. Affective responses were assessed by the Feeling Scale (FS), Borg’s Rating of Perceived Exertion (RPE) and the Activation-Deactivation Adjective Checklist (AD ACL). Methods Multivariate structural equation modeling was used to estimate heritability of the affective responses during and after submaximal and maximal exercise and the (genetic) correlation with self-reported regular voluntary exercise behavior over the past year. Results Genetic factors explained 15% of the individual differences in FS responses during the cycle ergometer test, as well as 29% and 35% of the individual differences in RPE during the cycle ergometer and treadmill tests, respectively. For the AD ACL scales, heritability estimates ranged from 17% to 37% after submaximal exercise and from 12% to 37% after maximal exercise. Without exception, more positive affective responses were associated with higher amounts of regular exercise activity (.15 < r < .21) and this association was accounted for by an overlap in genetic factors influencing affective responding and exercise behavior. Conclusions We demonstrate low to moderate heritability estimates for the affective response during and after exercise and significant (genetic) associations with regular voluntary exercise behavior. These innate individual differences in the affective responses to exercise should be taken into account in interventions aiming to motivate adolescents to adopt and maintain regular exercise.

PurposeThe prognostic power of heart rate recovery (HRR) after exercise has been well established but the exact origin of individual differences in HRR remains unclear. This study aims to estimate the heritability of HRR and vagal rebound after maximal exercise in adolescents. Furthermore, the role of voluntary regular exercise behavior (EB) in HRR and vagal rebound is tested.Methods491 healthy adolescent twins and their siblings were recruited for maximal exercise testing, followed by a standardized cooldown with measurement of the electrocardiogram and respiratory frequency. Immediate and long-term HRR (HRR60 and HRR180) and vagal rebound (heart rate variability in the respiratory frequency range) were assessed 1 and 3 min after exercise. Multivariate twin modeling was used to estimate heritability of all measured variables and to compute the genetic contribution to their covariance.ResultsHeritability of HRR60, HRR180 and immediate and long-term vagal rebound is 60 % (95 % CI: 48–67), 65 % (95 % CI: 54–73), 23 % (95 % CI: 11–35) and 3 % (95 % CI: 0–11), respectively. We find evidence for two separate genetic factors with one factor influencing overall cardiac vagal control, including resting heart rate and respiratory sinus arrhythmia, and a specific factor for cardiac vagal exercise recovery. EB was only modestly associated with resting heart rate (r = −0.27) and HRR (rHRR60 = 0.10; rHRR180 = 0.19) with very high genetic contribution to these associations (88–91 %).ConclusionsIndividual differences in HRR and immediate vagal rebound can to a large extent be explained by genetic factors. These innate cardiac vagal exercise recovery factors partly reflect the effects of heritable differences in EB.

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