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European Heart Journal Advance Access originally published online on January 22, 2007
European Heart Journal 2007 28(3):345-353; doi:10.1093/eurheartj/ehl468
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Reduced right ventricular ejection fraction in endurance athletes presenting with ventricular arrhythmias: a quantitative angiographic assessment

Joris Ector, Javier Ganame, Nico van der Merwe, Bert Adriaenssens, Laurent Pison, Rik Willems, Marc Gewillig and Hein Heidbüchel*

Department of Cardiology, University Hospital Gasthuisberg, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium

Received 4 November 2006; revised 13 November 2006; accepted 14 December 2006; online publish-ahead-of-print 22 January 2007.

* Corresponding author. Tel: +32 16 34 34 69; fax: +32 16 34 42 40. E-mail address: hein.heidbuchel{at}uz.kuleuven.ac.be


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Study limitations
 Conclusions
 Acknowledgements
 References
 
Aims Spontaneous or inducible sustained ventricular arrhythmias (VA) in endurance athletes frequently originate from the right ventricle (RV), even in the absence of familial arrhythmogenic RV cardiomyopathy (ARVC). The goal of this study was to determine whether the RV arrhythmogenic predilection in these patients is associated with RV functional abnormalities.

Methods and results Biplane RV angiography was performed in three groups: 22 endurance athletes with VA, 15 matched athletes without VA, and 10 non-athletes without VA. Four methods for quantitative RV angiographic analysis (area length, Boak, pyramid monoplane, and pyramid biplane) were used to calculate RV end-diastolic volume (EDV) and end-systolic volume (ESV) (both corrected for body surface area) and ejection fraction (EF). In addition RV outflow tract shortening fraction (SF) was determined. Although only 6 of 22 (27%) athletes with VA fulfilled the diagnostic criteria for ARVC, RV arrhythmogenic involvement was manifest or probable in 82%, based on a combination of electrophysiologic, electrocardiographic, and morphologic criteria. RV EDV in athletes was higher than in non-athletes (area length: 100.3 ± 26.9 vs. 69.6 ± 14.3 mL/m2, P = 0.001), without significant difference between athletes with and without VA. RV ESV, in contrast, was significantly higher in athletes with VA than in athletes without VA (52.6 ± 22.3 vs. 35.5 ± 11.2 mL/m2, P = 0.004), resulting in a significantly lower RV EF, a consistent finding across all methods (area length: 49.1 ± 10.4 vs. 63.7 ± 6.4%, P < 0.001). This functional impairment was also reflected in a lower RV outflow tract SF (SF right anterior oblique 32.2 ± 10.1 vs. 40.0 ± 11.6%, P = 0.09; SF left anterior oblique (LAO) 31.9 ± 7.8 vs. 39.0 ± 10.5%, P = 0.10).

Conclusion VA in high-level endurance athletes frequently originate from a mildly dysfunctional RV. This raises the question whether endurance exercise not only acts as a trigger for these arrhythmias but also as promoter of the RV changes.

Key Words: Athletes • Arrhythmia • Right ventricular function • Cineangiography


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Study limitations
 Conclusions
 Acknowledgements
 References
 
Athletic activity is associated with an increased risk of sudden cardiac death,1,2 with a relative risk of 2.5 when compared with non-athletes.3 Different underlying cardiovascular disorders constitute a predisposed setting for arrhythmias which are triggered by sports activity. In athletes younger than 35 years, hypertrophic cardiomyopathy and coronary anomalies are the most common conditions associated with sudden death, while ischaemic heart disease is the predominant cause above 35 years of age.1 Other authors pointed to underlying arrhythmogenic right ventricular cardiomyopathy (ARVC) as the principal cause of sports-related cardiac arrest in the Italian Veneto region.4

We reported on 46 symptomatic high-level endurance athletes (mainly cyclists) presenting with frequent and complex ventricular arrhythmias (VA).5 Sudden death occurred in 9 of 46 athletes (19.6%) during a median follow-up of 4.7 years. The induction of sustained VA during invasive electrophysiologic testing and arrhythmias based on re-entry were associated with a worse prognosis. We observed an unexpectedly high prevalence of right ventricular (RV) arrhythmogenic involvement (manifest in 59%, suggestive in 30%) which led to the hypothesis of a possible relationship between high-level endurance sports and RV modifications underlying the observed arrhythmias.

The aim of the present study was to determine whether the RV arrhythmogenic involvement in athletes with VA is accompanied by RV functional impairment. For this purpose, we performed quantitative angiographic assessment of RV volumes and ejection fraction (EF) in high-level endurance athletes with VA, matched athletes without VA, and controls. Given the complexity of RV volume and functional measurements, four different validated methods for RV angiographic analysis6–9 were used to assess differences in calculation methods and robustness of findings.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Study limitations
 Conclusions
 Acknowledgements
 References
 
Study population
The study comprised groups of endurance athletes with VA (n = 22), endurance athletes without VA (n = 15), and a control group of non-athletes without VA (n = 10). All athletes referred for electrophysiological evaluation of VA between July 1997 and April 2005 formed the basis of this study. Only male patients between 18 and 55 years of age were considered for inclusion. Patients with conditions possibly affecting RV function (e.g. ischaemic heart disease, atrial septal defect, pulmonary hypertension, and valvular heart disease) were excluded from the study, as were patients who were not in sinus rhythm at the time of electrophysiologic testing.

‘Athletes’ were considered only those who participated regularly in intense endurance sports i.e. ≥ 3 x 2 h/week for ≥ 5 years. All athletes meeting the inclusion criteria underwent evaluation with RV angiography. Athletes with VA had a history of symptomatic and documented sustained or non-sustained (>3 beats at > 100/min) ventricular tachycardia (VT; n = 20) or ventricular fibrillation (n = 2). From August 2002, also athletes without VA meeting the same inclusion criteria were consecutively included for RV angiography (n = 16). Athletes without VA were referred for electrophysiological evaluation for reasons other than VA, most commonly ablation for supraventricular arrhythmias. RV angiographic data analysis was not possible in two athletes with VA and one athlete without VA, due to excessive ventricular premature beats during contrast infusion. Final data analysis, therefore, included 22 athletes with VA and 15 athletes without VA. Cyclists and kayakers, who are known to have cardiac adaptations of mixed static and dynamic exercise,10 represented 76% of the athletes population. RV angiography was additionally performed in 10 randomly selected patients who did not regularly perform exercise and who were referred for electrophysiological evaluation of paroxysmal supraventricular tachycardia (‘controls’). Patient characteristics are summarized in Table 1.


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  		Table 1 Patient characteristics

 
Electrophysiological study and RV angiography
All antiarrhythmic agents were stopped for a period of five half-lives before the procedure. Angiography of the RV was performed in the baseline state (i.e. without infusion of adrenergic agonists). Images were recorded with digital biplane fluoroscopy (Bicor, Siemens, Erlangen, Germany) in both right anterior oblique (RAO) and LAO views. Standard 30° RAO/60° LAO fluoroscopic view-angles were adjusted to the intracardiac catheter positions as outlined before.11 Mean fluoroscopic RAO/LAO view angles, after adjustment, were 39 ± 5/51 ± 5° for athletes with VA, 42 ± 5/48 ± 6° for athletes without VA and 43 ± 6/48 ± 6° for non-athletes (P = NS). Forty millilitre of tri-iodinated, non-ionic contrast agent (Iomeron 350, Bracco Imaging SpA, Milan, Italy) was administered through a 7F pigtail catheter located near the RV apex at an infusion rate of 18 mL/s. Ventricular stimulation protocols were standard, consisting of fixed rate pacing (at cycle lengths down to 240 ms) and delivery of up to three extrastimuli at basic cycle lengths of 600 and 400 ms, both in the RV apex and outflow tract (down to the refractory period but never < 180 ms). A similar stimulation protocol was applied during isoproterenol infusion (1–4 µg/min) if the baseline study was negative. Only induction of monomorphic VT was considered specific under these latter conditions.

Quantitative angiographic analysis
Calculation of RV volumes, EF, and outflow-tract shortening fraction (SF) was performed with a novel software application (RV Analysis, Pie Medical Imaging, Maastricht, The Netherlands).12 Angiographic end-diastolic (ED) and end-systolic (ES) RV endocardial contours and pulmonary valve positions were manually outlined in RAO and LAO projections to allow for calculation of RV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and EF (Figure 1). Image calibration was performed by semi-automatically marking the width of a 7F catheter in RAO and LAO views. Volumes were calculated based on three different geometrical models with their own regression formulas to correct for each assumed mathematical shape (area length model, Boak model, and pyramid monoplane/biplane model6–9).


Figure 4681
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  		Figure 1 (A) Manual outlining of RV endocardial ED and ES contours in RAO and LAO angiographic views. (B) RV ED, ES, SV, and EF are calculated using one of the available geometrical models. Depicted results in this example are for area length method (Bi: biplane method; Mo: monoplane method).

 
ED, ES, and SV indices were calculated by dividing EDV, ESV, and SV by body surface area. Manual outlining of endocardial contours and calculations of volumes and EF were performed twice by the same operator to assess intra-observer variability. The mean of these two measurements was used for comparison of RV volumes and EF between different geometrical models and between different patient groups. The same procedure was repeated by a second operator to assess inter-observer variability. RV outflow-tract SF was determined by measuring ED and ES RV outflow-tract diameters in RAO and LAO views using the same image calibration. The SF was defined as the ratio of diastolic-to-systolic diameter-difference to ED diameter. Care was taken not to use post-ectopic ventricular contractions in the measurements.

Echocardiography, cardiac magnetic resonance imaging, and coronary angiography
Transthoracic echocardiograms were performed in all patients; wall thickness was measured and LV EF was calculated according to the American Society of Echocardiography guidelines.13 Cardiac magnetic resonance imaging (MRI) exams with steady-state free-precession cine sequences and T1-weighted turbo spin-echo images were available in 19 of 22 athletes with VA but in none of the patients without VA, precluding their use for quantitative comparison of RV function. A coronary angiogram was performed in 17/22 athletes with VA to exclude atherosclerotic heart disease. The remaining five athletes with VA, all younger than 30 years, underwent stress testing to exclude ischaemic heart disease.

Statistical analysis
Summary values are given as mean ± SD or median (range) for non-normally distributed values. Comparisons between the three patient groups were made by one-way analysis of variance with Scheffe's post hoc analysis. Differences in proportions between groups were evaluated with Fisher's exact test. A P-value < 0.05 was considered significant. Intra- and inter-observer variability were assessed by calculating the absolute differences between two subsequent and inter-individual measurements, respectively. Absolute differences were subjected to Bland-Altman analysis by calculating the mean difference and the limits of agreement (2SD around the mean difference).14 Receiver operating characteristic (ROC) curves were constructed and area under the ROC curves calculated to identify the best angiographic method to distinguish athletes with VA from athletes without VA based on RV function.15


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Study limitations
 Conclusions
 Acknowledgements
 References
 
Patient characteristics
Both athlete groups were matched for age, type, and intensity of sports (Table 1). The control patients were slightly older. Prior use of beta-blocking agents and antiarrhythmic drugs was somewhat higher in the control patients, but as mentioned, the EP study and RV angiography were performed after full wash-out of the drugs (except amiodarone in one control). All 22 athletes with VA had a history of symptomatic and documented VA. Symptoms were palpitations in two, palpitations with associated dizziness/pre-syncope in 12, syncope in six, and sudden death in two. The documented spontaneous VA was sustained monomorphic VT in nine patients, non-sustained monomorphic VT in four, non-sustained polymorphic VT in seven, and ventricular fibrillation in two. A history of frequent ventricular premature beats was present in 11 of 22 (50%) patients. Based on the diagnostic criteria defined by a task force of the European Society of Cardiology and International Society and Federation of Cardiology16 (including qualitative but not quantitative RV evaluation), the diagnosis of classical ARVC could be established in only six of 22 athletes (by one major and two or more minor criteria in five patients and by four minor criteria in one patient).

Sustained VA were induced during the electrophysiologic study in 14/22 (64%) athletes with VA. In 10 out of 14 (71%), the induced arrhythmia was monomorphic VT, always with a left bundle branch morphology. In four (29%), polymorphic VT was induced. Multiple monomorphic left bundle branch VT patterns were seen in four patients, resulting in a total of 19 VTs/14 patients. Mean VT cycle length was 267 ± 37 ms. VT was induced with one or two extrastimuli in 10/14 patients; three extrastimuli were required in only four patients and infusion of isoproterenol in two patients with a manifest automatic RV focus. Patients who had sustained monomorphic VT as presenting symptom were more likely to have inducible sustained VT after programmed ventricular stimulation than patients who presented with non-sustained VA, although this difference was not statistically significant (proportions 0.89 vs. 0.46, P = 0.07).

Based on a combination of electrocardiographic, electrophysiologic, and morphologic (MRI/biopsy) criteria5, an RV origin of the arrhythmia and/or arrhythmogenic substrate was manifest in 12/22 (55%) and probable in 6/22 (27%; sum = 82%). A focal arrhythmia mechanism was suspected in 10 patients (45%) by the presence of frequent spontaneous monomorphic or multiple monomorphic premature ventricular contractions or runs of premature ventricular contractions with variable coupling intervals and shortening of the cycle length with increasing adrenergic tone, and/or with a morphology typical for ‘idiopathic’ right ventricular outflow tract VT. Re-entrant arrhythmias were identified in eight patients (36%) by classical criteria during the EP study, like reproducible inducibility by extrastimuli (with a constant or increasing return cycle with decreasing coupling interval), resetting by extrastimuli, entrainment with (concealed) fusion and/or termination by programmed ventricular stimulation. The arrhythmia mechanism was unclear in four patients (18%).

Findings from RV evaluation with cardiac MRI (n = 19) and transthoracic echocardiography (n = 22) in athletes with VA are summarized in Table 2. Cardiac MRI showed regional basal or apical RV hypokinesia in three athletes with VA and global RV hypokinesia in two athletes with VA. However, T1-weighted images did not show evidence of fibrofatty infiltration of the RV myocardium in any of the patients. The diagnosis of ARVC was suggested in the MRI report of two athletes with VA based on global RV hypokinesia. Minor RV abnormalities (e.g. possible regional hypokinesia/wall thinning) were found in 6/19 athletes with VA while no MRI abnormalities were reported in 11/19 athletes with VA. Echocardiographic RV evaluation was normal in 18/22 athletes with VA, while severe RV dilation or global RV hypokinesia was considered suggestive of ARVC in two athletes with VA.


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  		Table 2 RV functional and morphological abnormalities in athletes with VA based on cardiac MRI and transthoracic echocardiography

 
There was no evidence of hypertrophic cardiomyopathy as the underlying arrhythmogenic substrate in any of the athletes with VA (echocardiographic septal wall thickness ≤ 14 mm in all). Of note, the echocardiographic LV EF was not different between both athlete groups (Table 1). Coronary angiography was normal in all but one athlete with VA, who had a 40% stenosis on the right coronary artery (RCA) without electrocardiographic or scintigraphic signs of ischemia during exercise testing.

A systematic screening of first-degree family members (brothers, sisters, and parents) was done in all athletes with VA and revealed no familial cases of ARVC. There was a familial history of sudden death or VA in two of 22 athletes, but no pre- or post-mortem documentation of the underlying cardiac substrate was available.

RV volumes and EF
Mild regional hypokinesia on angiography was present in six of 22 athletes with VA (three in the anterior RV wall, two in the RV outflow tract, and one in the basal portion of the RV) and none of the athletes without VA or controls. We did not observe localized RV aneurysms or severe segmental dilation of the RV in any patient. RV EDV index in athletes was significantly higher than in non-athletes (area length method 100.3 ± 26.9 vs. 69.6 ± 14.3 mL/m2, P = 0.001) but there was no significant difference between athletes with and without VA. On the other hand, ESV index was significantly higher in those with VA (area length method 52.6 ± 22.3 vs. 35.5 ± 11.2 mL/m2, P = 0.018). These findings were consistent across all angiographic methods (Figure 2). Accordingly, athletes with VA had significantly lower RV EF than athletes without VA (area length method 49.1 ± 10.4 vs. 63.7 ± 6.4%, P < 0.001) (Figure 3). This significance remained when the two athletes with VA and a familial history of arrhythmias or sudden death (i.e. presumed familial ARVC) were excluded.


Figure 4682
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  		Figure 2 RV volume measurements in athletes with VA, athletes, and non-athletes without VA, using four different geometrical models (area length, Boak, pyramid monoplane, and biplane as indicated). Athletes with VA have a significantly higher ESV than athletes without VA.

 

Figure 4683
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  		Figure 3 RV EF of athletes with VA, athletes, and non-athletes without VA measured using four different geometrical models (area length, Boak, pyramid monoplane, and pyramid biplane methods). There is a highly significant reduction of RV EF in athletes with VA.

 
There were no significant differences in RV EF or RV volumes between patients with arrhythmias based on re-entry vs. automaticity (n = 8 vs. 10), nor between patients in whom VA were induced during the electrophysiological study and those who were not inducible (n = 14 vs. 8).

The diagnostic value of different angiographic methods to identify athletes with VA in our study population was calculated from the area under the ROC curves (Figure 4). The area length method showed the highest area under the ROC curve (0.88, 95% CI 0.76–0.99). Its sensitivity and specificity to identify athletes with VA based on RV EF is shown for different RV EF cut-off values in Table 2. When using a RV EF cut-off value of < 55%, athletes with VA were identified in our study population with a sensitivity and specificity of 0.82 (0.60–0.95) and 0.93 (0.68–1.0), respectively, whereas an RV EF cut-off < 40% yielded a sensitivity of only 0.10 (0.001–0.23). This illustrates that reduction in RV EF in athletes with VA, however consistently present, was only mild and therefore not easily recognized without quantitative angiographic analysis.


Figure 4684
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  		Figure 4 Diagnostic value of different methods for quantitative RV angiographic assessment to identify athletes with VA. Left: Diagnostic value (AUC: area under the curve) of angiographic measurements to identify athletes with VA in our study population. The area length method has the highest area under the ROC curve and its sensitivity and specificity to identify athletes with VA at different RV EF cut-off values are represented in the box on the right. Cut-off values combining high sensitivity and specificity are marked in gray.

 
Consistency among different angiographic methods
RV EF measurements showed an excellent agreement between all biplane angiographic methods (Figure 3). EDV- and ESV-volume indices, however, showed a substantial variability between methods, with in general smaller volumes resulting from the area length calculation method (Figure 2). Intra- and inter-observer variability of absolute volume measurements (EDV, ESV) was considerable for all methods (Table 3). Again, the variability of RV EF measurements was much lower and certainly acceptable, with mean measurement differences of 1 ± 5% intra- and 0 ± 5% inter-observer. Bland-Altman plots demonstrated an equal variability for low and high values of EF and EDV (not shown). We considered the area length as the RV angiographic method of choice, based on the smallest intra- and inter-observer variability, and the largest area under the ROC curve.


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  		Table 3 Intra- and inter-observer variability of RV EF and EDV measurements

 
RV outflow tract SF
RV functional impairment in athletes with VA vs. athletes without VA was also reflected in a non-significant trend towards diminished RV outflow tract SF in both RAO and LAO views (SF RAO 32.2 ± 10.1 vs. 40.0 ± 11.6%, P = 0.09; SF LAO 31.9 ± 7.8 vs. 39.0 ± 10.5%, P = 0.10). The ROC curves of RAO SF and the area length method are represented in Figure 5: it illustrates the higher diagnostic value of the planimetric method calculating RV EF.


Figure 4685
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  		Figure 5 ROC curves representing sensitivity vs. specificity in classifying athletes as having symptomatic VA based on their RV function, plotted for area length method and RAO SF. Cut-off values combining maximal sensitivity and specificity are represented on the curves as a large circle/square. Area under the ROC curve is larger for the biplane angiographic area length method (0.88 vs. 0.71), reflecting its superiority to the monoplane RAO SF measurement.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Study limitations
 Conclusions
 Acknowledgements
 References
 
Our study clearly demonstrates RV functional abnormalities in high-level endurance athletes referred for electrophysiological evaluation of symptomatic VA. Moreover, the present and previous5 studies show a frequent RV arrhythmogenic origin in this particular patient population, with exclusion of other common arrhythmogenic causes such as coronary disease or hypertrophic cardiomyopathy as well as other diseases that could explain RV dysfunction.

An MRI study of 21 male endurance athletes by Scharhag et al.17 has shown that the normal response to intensive endurance training is a balanced hypertrophy of the heart, with an increase of RV volume (by 25 ± 9%) but with a preserved RV EF (63 ± 3%). Comparable to their results, our study showed a RV EF of 64 ± 6% in athletes without VA. The reduced RV EF (49 ± 10%) observed in athletes with VA can therefore not be attributed to the presence of athlete's heart per se, as both athlete groups participated in sports activity with the same intensity and frequency.

Although ARVC was reported to be the cause of sudden cardiac death in 6–27% of athletes in the Italian Veneto region,18,19 the overt characteristics of this disease were absent in the majority of our patient population. When the diagnostic criteria for ARVC16 were applied, only 6/22 (27%) of athletes with VA were classified as having ARVC. Also, only two of 22 athletes had a positive familial history. Invasive electrophysiological evaluation combined with electrocardiographic and morphologic data however pointed to a probable or manifest RV arrhythmogenic origin in 82% of the athletes with VA.

Two hypotheses could explain the observations of RV arrhythmogenic involvement and RV functional changes in athletes with VA: (i) ARVC is detected during an early stage in these high-level endurance athletes, causing VA in a phase where RV function is only moderately impaired and the overt characteristics of ARVC are absent, or (ii) high-level endurance exercise promoted RV structural remodelling (and VA), implying a causative role of endurance exercise per se.

When considering the first hypothesis, one has to be aware that the differences in RV EF between athletes with and without VA or controls in our study are subtle (50 vs. 60–65%) and not easily recognized without quantitative analysis of RV angiograms. A previous angiographic study reported a RV EF of < 35% in 27/85 (32%) of patients with ARVC,20 indicating more pronounced RV structural disease in non-athletes diagnosed with ARVC. Also, the absence of familial forms in all but two athletes in our series and the absence of RV fibrofatty replacement on MRI are contrasting with ‘classical’ ARVC, as described in non-athletes. The fact that only six of 22 athletes with VA fulfilled the diagnostic criteria for ARVC, would also imply insufficient sensitivity of the classical criteria to diagnose such early forms of ARVC, as has also been shown for early or mild disease expression in relatives of patients with familial ARVC.21

The hypothesis of high-level endurance exercise as primary underlying pathophysiological cause is more controversial, and unequivocal evidence proving such a long-term detrimental effect of endurance exercise is lacking. There are, however, different reports demonstrating the higher loading conditions on the right than on the LV during endurance sports. Human experimental studies have shown a greater increase in stroke work in the RV than in the LV during exercise,22–26 and different echocardiographic reports have shown transient selective RV dilatation and/or a decreased RV function in athletes immediately after endurance athletic events.27,28 Moreover, chronic volume overload has been shown to cause a greater mass increase in the RV than in the LV and to result in an increased collagen deposition and selective growth factor activation restricted to the RV in animal models.29,30

These findings suggest that endurance exercise and volume overload subject the thin-walled RV to a greater increase in workload than the thick-walled LV with subsequent different remodelling. In this respect, it may be of particular interest that cyclists and a kayaker, who have both high dynamic and static loading10 represented more than 80% of our population of endurance athletes.

Interestingly, recent insights in the genetic etiology of inherited ARVC also point towards an important role of RV mechanical loading conditions.31 Most disease-causing genes identified in ARVC encode desmosomal proteins that anchor intermediate filaments between adjoining myocardial cells. Impaired function of these cell adhesion junctions during exposure to shear stress may lead to myocyte detachment and death, accompanied by inflammation and fibrofatty repair. According to this model, predilection of ARVC to the RV can be explained by the increased distensibility of the thin-walled RV, with the thinnest portions being affected in the earlier stages due to increased wall tensions (triangle of dysplasia). Similarly, genetic predisposition, possibly by an unidentified genetic polymorphism, may make cell-adhesion in some athletes more vulnerable to shear stress becoming only clinically apparent under the high loading conditions of endurance exercise. Such a detrimental effect of endurance training has recently been proven in a mouse model of ARVC in which endurance training accelerated the development of RV dysfunction and arrhythmias in heterozygous plakoglobin-deficient mice.32

Angiographic evaluation of RV volumes and EF is challenging due to the complex shape of the RV. The calculation of these parameters in our study was performed with four different methods that were validated in heart-cast studies.6–9 We observed a substantial variability in calculated volumes between methods, but the observed differences among patient groups were consistent. The main findings of our study, i.e. a mildly reduced RV EF and elevated ESV in athletes with VA vs. athletes without VA, were consistently found with each method. Angiography can easily be performed during an electrophysiological study in patients presenting with VA. On the other hand, modern imaging technologies such as cardiac MRI have the potential to yield more accurate volume and EF determinations and will probably replace RV angiography in the future.

When using a RV EF cut-off value of < 55%, athletes with VA were identified in our study population with a maximal sensitivity and specificity of 0.82 (0.60–0.95) and 0.93 (0.68–1.0), respectively. However, given the limited patient numbers, this calculated cut-off value is only applicable to the population on which it was calculated and cannot be easily generalized to the entire population of high-level endurance athletes.33


   Study limitations
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Study limitations
Conclusions
 Acknowledgements
 References
 
Fluoroscopic view-angles for angiography were not adjusted to the view angles for which different volume calculation methods were developed. However, differences in results for RV EF and volumes due to the difference in view angles were very small. This is also illustrated by the small differences between the results of the area length and Boak method, the first of which could be adapted to 45°RAO/45°LAO view angles in contrast to the second method. The larger intra- and inter-observer variability for absolute volume measurements when compared with RV EF measurements is most probably caused by the semi-automatic image calibration method based on catheter diameters. A calibration method based on a larger calibration object might reduce this calibration error.

Although cardiac MRI was performed in 19 of 22 athletes with VA, quantitative MRI data on RV volumes and EF were not available and therefore could not be compared with angiographic measurements. The lack of quantitative MRI data on RV function and volumes was primarily caused by the fact that no significant MRI abnormalities were found in the majority of athletes with VA and further RV quantitative assessment was therefore omitted. A systematic quantitative RV evaluation in athletes with and without VA would have allowed for MRI validation of our angiographic data.

RV biopsy for pathological examination was performed in only five athletes with VA and showed no specific light-microscopic abnormalities suggestive of ARVC. Transmission electron microscopy was not performed to look for ultrastructural evidence of intercalated discs remodelling34 in athletes with VA. Such studies will be important to investigate possible (ultra) structural changes that underlie the functional abnormalities.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Study limitations
 Conclusions
Acknowledgements
 References
 
VA in high-level endurance athletes often originate in the RV. Quantitative RV functional evaluation in these athletes shows a similar RV EDV when compared with athletes without VA, but a significantly lower RV EF. The observed dysfunction is more subtle than in familial or overt ARVC (which was only present in a minority by conventional criteria). This raises the question whether exercise in these athletes acted merely as a trigger for arrhythmias in an early stage of underlying ARVC, or whether exercise also acted as a promoter of the RV changes (maybe in synergy with other environmental or genetic factors).


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Study limitations
 Conclusions
 Acknowledgements
References
 
J.E. is a research assistant and H.H. is a Fundamental Clinical Investigator of the Fund for Scientific Research—Flanders. H.H. is holder of the AstraZeneca Chair in Cardiac Electrophysiology, University of Leuven.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Study limitations
 Conclusions
 Acknowledgements
 References
 

  1. Maron BJ, Shirani J, Poliac LC, Mathenge R, Roberts WC, Mueller FO. (1996) Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA 276:199–204.[Abstract]
  2. Maron BJ. (2003) Sudden death in young athletes. N Engl J Med 349:1064–1075.[Free Full Text]
  3. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. (2003) Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol 42:1959–1963.[Abstract/Free Full Text]
  4. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. (2003) Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol 42:1959–1963.[Abstract/Free Full Text]
  5. Heidbuchel H, Hoogsteen J, Fagard R, Vanhees L, Ector H, Willems R, Van LJ. (2003) High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification. Eur Heart J 24:1473–1480.[Abstract/Free Full Text]
  6. Ferlinz J, Gorlin R, Cohn PF, Herman MV. (1975) Right ventricular performance in patients with coronary artery disease. Circulation 52:608–615.
  7. Ferlinz J. (1977) Measurements of right ventricular volumes in man from single plane cineangiograms. A comparison to the biplane approach. Am Heart J 94:87–90.[CrossRef][ISI][Medline]
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