Anabolic Steroid Abuse and Cardiac Sudden Death

A Pathologic Study

Vittorio Fineschi, MD, PhD; Giorgio Baroldi, MD; Floriana Monciotti, MD; Laura Paglicci Reattelli, MD; Emanuela Turillazzi, MD, PhD

From the Division of Forensic Medicine, University of Foggia, Italy (Drs Fineschi and Turillazzi); the Institute of Clinical Physiology, National Research Council, University of Milan, Italy (Dr Baroldi); the Division of Forensic Medicine, University of Siena, Italy (Dr Monciotti); and the Institute of Legal Medicine, University of Perugia, Italy (Dr Reattelli).

Context.-Androgenic anabolic steroids (AAS) used for improving physical performance have been considered responsible for acute myocardial infarction and sudden cardiac death.

Objective.-To establish the relationship between AAS and cardiac death.

Design.-Case report.

Patients.-Two young, healthy, male bodybuilders using AAS.

Main Outcome Measures.-Pathologic cardiac findings associated with AAS ingestion.

Results.-The autopsy revealed normal coronary arteries. In one case, we documented a typical infarct with a histologic age of 2 weeks. A segmentation of myocardial cells at the intercalated disc level was observed in the noninfarcted region. This segmentation was the only anomaly detected in the second case. No other pathologic findings in the heart or other organs were found. Urine in both subjects contained the metabolites of nortestosterone and stanozolol.

Comment.-A myocardial infarct without vascular lesions is rare. To our knowledge, its association with AAS use, bodybuilding, or both lacks any evidence of a cause-effect relationship. The histologic findings in our 2 cases and in the few others reported in medical literature are nonspecific and do not prove the cardiac toxicity of AAS. A better understanding of AAS action on the neurogenic control of the cardiac function in relation to regional myocardial contraction and vascular regulation is required.

Androgenic anabolic steroids (AAS) are used worldwide to help athletes gain muscle mass and strength. They are beneficial in athletic competition and are particularly beneficial for power lifters, bodybuilders, student athletes, and fitness enthusiasts. The real incidence is difficult to evaluate, but a recent study indicated that more than 1 million Americans are current or former users. The intake of these steroids has been associated with vascular complications, cardiomyopathy, coronary atherosclerosis, and cardiac hypertrophy, and in several clinical reports, intake was associated with an acute myocardial infarct. However, to our knowledge, only 7 sudden cardiac death cases have been examined after the patient's death. In 2 other sudden-death cases, the cause at autopsy was imputed to be pulmonary venous thrombosis. A right cerebellar hemorrhage spreading into the pons and ventricular systems was the cause of death in another case. In the latter case, a histologic examination of the heart revealed an area of fibrosis in the inferior myocardium that was consistent with an old myocardial infarction; coronary arteries were normal.

This article discusses 2 sudden death cases in healthy bodybuilders who were using androgenic anabolic steroids. The cardiac pathologic findings are analyzed.

REPORT OF CASES

Case 1

A 32-year-old bodybuilder suddenly lost consciousness during a weight lifting workout at the gymnasium. After an unsuccessful resuscitation attempt, he was pronounced dead because of an instantaneous cardiac arrest. Two weeks earlier, he had experienced an episode of chest pain that lasted a few minutes, with pain radiating to his left arm. According to relatives and friends, the patient did not consult a doctor and continued his training, believing that the pain was caused by his physical activity. For several months he was taking testosterone propionate (700 mg/ wk) and nandrolone (200 mg/wk) parenterally, and he was taking stanozolol per os (70 mg/wk). His medical history was unremarkable.

Postmortem Findings.-The body was that of a well-built man (height 189 cm, weight 90 kg) with prominent muscular masses. The 450-g heart was normal in shape, with no cavity dilatation. Its dimensions (14 × 14 × 4 cm) and wall thicknesses (17-mm left ventricle, 11-mm interventricular septum, and 5-mm right ventricle) all fell in the normal range. The heart weight as a percentage of body weight was 0.5%. The pericardium, cardiac valves, endocardium, and coronary arteries were normal. In particular, the latter and their major branches were cross-sectioned at 3-mm intervals, with no gross evidence of lesion or lumen reduction. The coronary arteries arose from normally located and patent ostia possessing normal anatomic disposition. The posterior descending branch originated from the right coronary artery. The myocardium was usual in appearance except for one grayish zone in the internal half of the anterior-lateral wall of the left ventricle. It corresponded to 20% of the whole left ventricular myocardial mass, including the interventricular septum. No thrombi were noted in the cardiac cavities. Ten samples of the coronary arteries; 2 of the atria; 8 of the anterior, lateral, and posterior left ventricle; and the anterior and posterior interventricular septum were taken for histologic examination and stained with hematoxylin-eosin and phosphotungstic acid hematoxylin.

Histologically, the grayish area corresponded to typical infarct necrosis with a histologic age of approximately 15 days. The lesion was characterized by dead, hyperdistended myocardial cells with sarcomeres in registered order, circumscribed at its periphery by young collagen tissue containing numerous macrophages. External to the infarct necrosis was a large layer of contraction band necrosis formed by hypercontracted, deeply eosinophilic myocardial cells with rupture of the myofibrillar apparatus in anomalous bands, with no macrophagic reaction. At other cardiac sites, the pathologic findings were represented by occasional foci of contraction band necrosis and few fibrotic microfoci in the internal portion of the posterior left ventricle and interventricular septum.

In all of the myocardial samples, segmentation of the myocardial cells at the intercalated disc level or widening of the cells at this level with bundles of distended myocardial cells alternating with bundles of contracted myocells was found. Granular disruption of the myocardial cells was occasionally observed. The coronary artery sections proved to be normal, with no evidence of any pathologic change. Both gross and histologic examinations of other organs did not reveal any pathology.

Case 2

A 29-year-old bodybuilder was found unconscious in bed one morning in his apartment. A cardiopulmonary resuscitation attempt, performed by a physician, was unsuccessful. According to his medical practitioner, he had no history of disease. Family members and friends reported that he had been using anabolic steroids parenterally (nandrolone 250 mg/wk and stanozolol 350 mg/wk) for several months.

Postmortem Findings.-The body was of a well-built man (weight 72 kg, height 166 cm). All organs were normal. In particular, the dimensions of the heart were 11 × 10 × 5 cm, the weight was 390 g (0.54% of body weight), and the wall thicknesses were 19 mm for the left ventricle, 13 mm for the interventricular septum, and 6 mm for the right ventricle. All of the cardiac components were normal, according to the previously described examinations. Histology did not reveal any pathologic changes in the extramural and intramural arterial vessels, valves, and epiendocardium. Only occasional, isolated myocardial cells with contraction bands and segmentation of the myocardial cells similar to those seen in the other case were noted.

Toxicologic Analysis

In neither case did urine screening detect cocaine, amphetamines, or other abused drugs. Gas chromatographic mass spectrography of urine showed 19-nor-androsterone, 19-nor-etiocholanolone, and nor-epiandrosterone (metabolites of nandrolone), as well as 3-idrossi-stanozolol and 3-idrossi-17-epistanozolol (metabolites of the anabolic steroid stanozolol) in both subjects.

COMMENT

The number of autopsy cases of sudden and unexpected death associated with AAS use is not sufficient to establish whether or not an AAS cardiotoxicity exists or to explain the mechanism of the sudden cardiac arrest.

In our cases, and in most of those reported in medical literature, lesions at any level of the coronary system were absent, even in the presence of a myocardial infarction. Our first case is the only one with histologically documented infarct necrosis among young athletes abusing AAS. Histologically, this silent or almost-silent infarct occurred approximately 2 weeks before the terminal episode and did not impede the athlete's habitual, vigorous physical training. The sudden cardiac arrest is most likely related to adrenergic stress, documented by the extensive, early contraction band necrosis and triggered by the terminal physical effort. The absence of lymphocytic infiltrates or myocardial fibrosis in our 2 cases supports the lack of a toxic effect both of AAS and other toxic factors linked with lymphocytic infiltration, as reported in 3 other cases. Lymphocytic infiltrates are rarely found in normal healthy subjects who die accidentally. Cardiac hypertrophy, in our cases, was minimal. This mild hypertrophy is probably related to the increased muscular mass after hard physical training.

Although, to our knowledge, no unifying hypothesis has emerged to account for the occurrence of these sudden cardiac deaths, it is possible to implicate many intravascular, vascular, and myocardial etiologies. Increases in total cholesterol occur with anabolic steroids, and this has been shown to augment the coronary artery response to catecholamines. Anabolic agents have also been shown to enhance this pressor response to catecholamines in rodents. Several animal studies have led to the speculation that AAS may interact with exercise-induced adaptations of the cardiovascular system to produce unfavorable effects. Sympathetic neurons, instrumental in nervous control of the cardiovascular system, may be affected by AAS administration when it is combined with exercise. Other studies have indicated that testosterone can both selectively inhibit extraneuronal uptake of neuroamines and increase the vascular response to norepinephrine.

The cause-effect relationship among AAS, bodybuilding, and myocardial infarction presently lacks solid evidence. However, the concept of cardiac arrest caused by catecholamine myotoxicity associated with ventricular fibrillation is suggested by (1) the finding of contraction band necrosis or disseminated focal necrosis, as encountered in other cases, and by (2) an experimental study in which AAS, administered in combination with exercise training, induced degenerative changes within the intracardiac sympathetic neurons of the mouse.

In conclusion, a more complete pathologic study with strict clinical case correlation of acute myocardial infarctions and AAS use is needed. In addition, we need more information regarding the role of AAS effect, particularly in relation to an adrenergic control, on the coronary vessels and myocardium.


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