Page not availableAn estimated 3 million to 4 million Americans have used anabolic-androgenic steroids testosterone or synthetic derivatives of testosterone ahabolic gain muscle mass for sports or to enhance their appearance. A large new study demonstrates that such use can narrow the coronary arteries and impair left ventricular LV function. Together, these effects can reduce the supply of oxygenated blood both to the heart and from the heart to the arteries. Aaron Baggish and colleagues at Massachusetts General Hospital in Boston and McLean Hospital in Belmont, Massachusetts, assessed the heart and coronary arteries long term anabolic androgenic steroid use is associated with left ventricular dysfunction male weightlifters ages 34 to All the men could bench-press pounds at some point in their lives; 58 were currently using AAS; 28 had previously used AAS angry birds space eggsteroid levels at least 2 years; and 54 had never used AAS.
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This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids AAS on atrial electromechanical delay AEMD in male bodybuilders.
We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders.
Self-administration of high doses of anabolic androgenic steroids AAS is a widespread practice among athletes to increase lean body mass and muscular strength. Long-term illicit use of supraphysiologic doses of AAS may cause several adverse cardiovascular effects [ 1 — 4 ]. Recent studies have found pathological left ventricular LV hypertrophy, diastolic dysfunction, and subclinical LV systolic impairment in long-term AAS users [ 4 — 7 ].
In addition, ventricular and atrial arrhythmic events were described secondary to the intake of AAS. Atrial fibrillation AF is the most frequently observed arrhythmia in bodybuilders who are using AAS [ 8 ].
However, the mechanisms underlying such predispositions to AF are poorly understood and also it is not clear that AAS using athletes are more prone to atrial rhythm disturbances than non-AAS users. The prolongation of intra-atrial and interatrial conduction times and the inhomogeneous propagation of sinus impulses are typical electrophysiological features of the atrium which is prone to fibrillate [ 12 , 13 ].
Since AF is a reentrant arrhythmia, it is logical that the triggering factor generally is a critically timed atrial activation that may give rise to reentry in a vulnerable structure [ 16 ]. Atrial and ventricular structural alteration, increased atrial stretch, autonomic imbalance, atrial interstitial fibrosis, inflammation, and ischemia may act in this respect as an internal or external factor by modulating atrial refractoriness through both atria and modifying intra-atrial conduction [ 17 — 19 ].
Therefore, we attempted to investigate atrial conduction abnormalities in AAS using athletes and to compare those of non-AAS users by using electromechanical coupling interval and TDI. We selected a population of 33 competitive bodybuilders, including 15 who actively used AAS for 2 years users and 18 who had never used AAS nonusers , all men.
Written informed consent was obtained from each subject, and the study was approved by the appropriate institutional ethics review committee. Exclusion criteria were presence of coronary artery disease, valvular or congenital heart disease, hypertension, congestive heart failure, diabetes mellitus, sinus tachycardia, psychiatric, respiratory, or metabolic disorders, inadequate echocardiographic quality, and smoking habit.
AAS users and nonusers had started bodybuilding at approximately the same age versus years, resp. Additionally, urine testing was performed by high-performance liquid chromatography coupled to mass spectrometry to confirm or exclude any recent consumption of anabolic steroids. The orally self-administered drugs were oxymetholone and stanozolol, and the injectable steroids were nandrolone, stanozolol, and testosterone propionate.
The mean duration of AAS use was years range, 4—20 years. All subjects were examined on an empty stomach. Venous blood samples were drawn from each subject, always in the afternoon between 1 and 2 PM, to evaluate serum hormone levels testosterone, luteinizing hormone, follicle-stimulating hormone, insulin, T3, and T4 , hematology hematocrit, hemoglobin , and blood lipids total cholesterol, high-density lipoprotein. Examinations were performed by a cardiologist who was blinded to the clinical details of each subject.
Single-lead ECG was recorded continuously during the echocardiographic examination. Two-dimensional, M-mode and tissue Doppler images were acquired from the parasternal long and short axis and apical four-chamber views at end-expiratory apnea and were transferred to customized dedicated software package EchoPAC, General Electric Vingmed Ultrasound for offline analysis of stored data.
All measurements were averaged from three cardiac cycles. Left atrium LA , LV dimensions, and wall thickness were obtained from the parasternal long axis with an M-mode cursor positioned just beyond the mitral leaflet tips, perpendicular to the long axis of the ventricle.
LV ejection fraction was calculated according to the Simpson method [ 22 ]. For determination of LVM, the Devereux formula was used: Left ventricular mass index was calculated by dividing LVM by body surface area.
LA areas and volumes were measured in the apical four-chamber and two-chamber views at ventricular end-systole maximum LA size and mean values of area and volume were obtained. LA mean volume was indexed to body surface area BSA [ 22 ]. Mitral inflow velocities were evaluated by pulsed-wave Doppler echocardiography with the sample volume placed at the tip of the mitral leaflets from the apical four-chamber view.
Diastolic peak early and peak late transmittal flow velocity, peak to peak velocities , and isovolumic relaxation time IVRT were measured [ 24 ]. Care was taken to align the echo image so that the annular motion was parallel to the TDI cursor. In apical 4-chamber view, the pulsed Doppler sample volume was subsequently placed at the level of LV lateral mitral annulus, septal mitral annulus, and right ventricular RV tricuspid annulus. The myocardial peak systolic and early diastolic velocity and late diastolic velocity were obtained from the septum, the lateral wall of the left ventricle, and the annulus of the right ventricle.
The Em global and Am global velocities were derived by averaging the velocities from the 2 mitral annular sites. Atrial electromechanical delay AEMD was measured as the interval between the onset of the P wave on the electrocardiogram and the beginning of late diastolic Am wave at the lateral mitral annulus PA atrial electromechanical coupling lateral , septal mitral annulus PA septum , and RV tricuspid annulus PA tricuspid.
Values were averaged over three consecutive beats. In AEMD measurements, intraobserver variability was assessed in 20 selected subjects at random from the patient study group by repeating the measurements under the same basal conditions. To test the interobserver variability, we performed the measurements offline from video recordings by a second observer. The intraobserver and interobserver variability for TDI calculated from 20 consecutive patients were 5.
Continuous variables are expressed as mean standard deviation and categorical data are expressed as percentages. Statistical comparison of quantitative data was performed by unpaired -test. Multiple regression analysis was used to identify significant predictors of inter- and intra-AMED. Thus, all predetermined independent variables that correlated with a value of less than 0.
A value of 0. All statistical studies were carried out with the SPSS program version The characteristics of the subjects are listed in Table 2. No differences between groups emerged from age, height, weight, BSA, blood pressure, or heart rate.
Table 3 shows the details of the echocardiographic analysis. LV mass index, interventricular septal thickness, LV posterior wall thickness, and relative diastolic wall thickness were significantly greater in AAS users than in nonusers and sedentary controls.
Transmitral Doppler echocardiography data of LV diastolic function are listed in Table 2. No significant differences were found in peak and peak between AAS users and nonusers. However, drug-using bodybuilders exhibited longer isovolumetric relaxation times and lower ratio of than their drug-free counterparts.
Global and were significant difference in ASS users compared to nonusers versus , ; versus , , resp. Table 4 shows the atrial electromechanical intervals measured at the lateral, septal, and RV annulus by the tissue Doppler method.
Interatrial and intra-atrial EMD values were significantly higher in the AAS using bodybuilders compared with those in the nonusers versus , ; versus , , resp. There was also correlation between global , global , and inter-AMED , ; , , resp. Furthermore, it has been reported that myocardial infarction, cardiomyopathy, sudden death, cardiovascular morbidity, and mortality have significantly increased in long-term AAS using bodybuilders more than nonusers [ 28 ].
In addition, arrhythmic events were described secondary to the long-term intake of AAS. Although AF is the most frequently observed arrhythmia, ventricular arrhythmias were also described [ 8 — 11 , 29 ].
However, it is not clear that AAS using bodybuilders are more prone to rhythm disturbances compared with nonusers. The prolongation of intra- and inter-AEMD and the inhomogeneous propagation of sinus impulses are well-known electrophysiologic characteristics of the atria which is prone to fibrillation [ 12 , 13 ]. Also, Roshanali and colleagues have found that atrial electromechanical interval is a predictor of AF emerging after coronary artery bypass grafting and demonstrated that the preoperative administration of amiodarone to patients having longer atrial electromechanical interval has decreased the postoperative atrial fibrillation incidence [ 33 ].
Furthermore, De Vos et al. There are several studies that indicate impairment of LV diastolic function, which is known to play a role in the pathogenesis of AF [ 17 , 34 , 35 ], which was also found to be impaired in AAS using athletes [ 4 — 7 ]. When left ventricular diastolic dysfunction occurs, emptying of the left atrium is impaired as well.
Following impaired left ventricular diastolic relaxation, there is increased atrial contribution to the mitral flow in the left ventricular diastolic flow, thus leading to atrial overstretching and enlargement [ 36 ]. The left atrium diameter is known to be correlated with cardiovascular events and is a risk factor for AF [ 37 ].
In this study, the left atrial diameters of the AAS user and nonuser groups were similar. However, the presence of left ventricular diastolic dysfunction in AAS user athletes is a controversial issue. Other authors did not find any difference in the diastolic function of strength athletes with or without AS abuse [ 40 — 42 ]. The studies mentioned above used two-dimensional echocardiography and Doppler measurements of transmitral blood flow to assess diastolic function.
In our study this technique was not able to show an altered diastolic function in AAS users too. We investigated the diastolic functions by using the tissue TDI method as well because the conventional Doppler method is load dependent and TDI constitutes a good index of LV relaxation properties.
In previous studies, the and were demonstrated to be significantly correlated with the left ventricle end-diastolic pressure and diastolic dysfunctions [ 24 , 44 ]. In our study, we found that ratio was significantly higher in AAS users than in nonusers. In addition, the ratio was significantly lower in AAS users than in nonusers. Furthermore, we found correlations between and and inter-AMED [ ; and ; , resp.
Therefore, we believe that this impairment in the diastolic function might be one of the reasons for the prolonged atrial conduction times in AAS using bodybuilders. LV pathological hypertrophy induced by AAS appears to be generated by a direct action on cardiac androgen receptors, whose effects are directly proportional to the doses, time, and duration of drug administration [ 4 ].
The presence of LV hypertrophy is an indicator of increased myocardial demand for oxygen and hence decreases coronary reserve. When coronary blood flow is fixed or reduced, there is a supply-demand mismatch, resulting in increased risk for ischemia. In such a scenario, a decrease in blood flow can be catastrophic to the already increased demand of the myocardial cells.
Patients with LV pathological hypertrophy are at increased risk for ischemia, probably causing prolongation of inter- and intra-AEMD [ 34 ]. Probably adverse effects of AAS on the cardiovascular system are also due to direct toxicity on myocardial structure with increased collagen deposition, fibrosis, and altered microcirculation with intimal hyperplasia of the intramural coronary arteries resulting in chronic ischemic damage [ 21 ].
Vascular endothelial cells may be directly affected by AAS, which may result in vasospasm [ 21 ]. As the cause of these alterations, AAS may directly affect the atrium, causing heterogeneity in the atrial conduction [ 20 , 21 ].
Therefore, we speculated that long-term illicit use of supraphysiologic doses of AAS might directly affect atrial conduction time inter-AMED. The last possible mechanism to increase AEMD may be sympathetic activation. It has been shown that chronic consumption of supraphysiologic doses of AAS induces cardiac autonomic imbalance by reduction in parasympathetic cardiac modulation and increase in sympathetic cardiac modulation [ 10 ].
Experimental studies showed that greater sympathetic activation leads to myocardial injury. Increased sympathetic activity may also trigger atrial arrhythmias [ 45 ]. Therefore, altered autonomic system regulation occurring secondary to the chronic consumption of supraphysiologic doses of AAS may be the other reason underlying the delayed interatrial electromechanical coupling intervals. Our study has several limitations. The most important limitations of our study are the small sample size and cross-sectional design of the study, in which we could not follow up the patients prospectively for future arrhythmic events.