Dr Arefzadeh Case Report
یکشنبه 27 شهریور‌ماه سال 1384
Case Report 1
Case  Report  1

                                                   Year-Old Man with Sudden Loss of Consciousness   whileJogging

Presentation of Case

An unidentified black man who appeared to be approximately 40 years of age was brought to the emergency department of this hospital after suddenly losing consciousness. Witnesses had seen the patient jogging, and then they saw him suddenly stop, arch his back, and fall backward to the ground, striking the back of his head. Personnel from emergency medical services found him lying supine on the ground, unconscious, with stertorous respirations.

At the scene, the respiratory rate was 36 breaths per minute, the blood pressure 140/110 mm Hg, and the pulse 120 beats per minute. The blood glucose level was 140 mg per deciliter. The man spontaneously flexed his right arm. Believing that this was a seizure, the emergency medical technicians administered 10 mg of diazepam intravenously. A cervical collar was placed, and he was transported to this hospital.

On arrival in the emergency department, the patient was unresponsive to verbal and physical stimulation. The temperature was 37.6°C, the blood pressure 116/71 mm Hg, the pulse 100 beats per minute, and the respiratory rate 24 breaths per minute. Oxygen saturation was 97 percent while the patient was receiving 100 percent oxygen through a mask attached to a bag-valve ventilation system.

On physical examination, there was a laceration, 3 cm in length, along the left parietal occipital region of the head. The pupils were 4 mm in diameter, equal, round and reactive to light. There was no sign of trauma to the face. There was no crepitus in the soft tissue of the neck, and the trachea was midline. The jugular venous pressure could not be assessed. No carotid bruits were heard. An examination of the chest, heart, and abdomen disclosed no abnormalities. Rectal tone was normal, and the stool was negative for occult blood. The patient's arms and legs were well perfused with normal pulses. There were no deformities of the spine and no evidence of trauma to his back.

On neurologic examination, the patient initially did not respond to voice stimulation or open his eyes spontaneously; shortly after arrival he began to respond to noxious stimuli. Bilateral corneal reflexes were present, and his face was symmetric. There was no nystagmus. The motor examination revealed withdrawal of all extremities from noxious stimuli. Reflexes were 2+ throughout, and the toes were turned down bilaterally.

An electrocardiogram obtained 20 minutes after the patient's arrival showed normal sinus rhythm, left ventricular hypertrophy, right bundle-branch block, and ST-segment depression in leads I, V4, V5, and V6, as well as T-wave inversion in leads I, aVL, and V4 to V6 (shown in Figure 1 of the Supplementary Appendix, available with the full text of this article at www.nejm.org). Computed tomography (CT) was then attempted, but the patient suddenly became agitated. Because he posed a risk to himself and was not able to cooperate fully with the imaging studies, the trachea was intubated with the use of lidocaine, etomidate, and succinylcholine. Vecuronium and midazalom were administered for extended paralysis. A gastric tube was placed. A radiograph of the chest was obtained with a portable unit and revealed that the endotracheal tube was correctly placed and there were no obvious pulmonary lesions.

Fifty minutes after the patient arrived, CT of the brain and cervical spine was performed without the administration of contrast material. The scanning revealed no intracranial hemorrhage and no fracture of the skull or cervical spine. There was a subgaleal hematoma over the left parietal bone. A CT scan of the abdomen performed after the intravenous administration of contrast material revealed a normal aorta with no sign of injury to the liver, kidneys, or spleen.

The complete blood count and levels of electrolytes and glucose, as well as the results of tests of coagulation, renal function, and liver function, were all within normal ranges. A rapid qualitative test of creatine kinase was borderline positive, and a rapid qualitative test of troponin T was negative. The toxicologic screening for alcohol, barbiturates, benzodiazepines, tricyclic antidepressants, opiates, and cocaine metabolites was negative. One gram of phenytoin was administered intravenously. The laceration was irrigated and sutured.

Approximately three hours after his arrival, the patient was identified by the local police, and his wife was located. She reported that one year earlier the patient had collapsed while jogging and had been taken to another hospital. The patient, an engineer from Cameroon, had been told to stop playing soccer because he had a "thickened" heart, and a beta-blocker had been prescribed.

A diagnostic procedure was performed.

Differential Diagnosis

Dr. William D. Binder: The presentation of an unidentified patient who has had a sudden loss of consciousness is a problem both familiar and perplexing to the emergency physician. Many diseases may be manifested clinically as a sudden loss of consciousness (Table 1).1,2 The emergency physician must quickly ascertain whether or not a patient has a life-threatening disorder and determine a course of action, often without vital historical information. We had to decide whether this patient's loss of consciousness was due to a transient or catastrophic neurologic problem, a cardiopulmonary problem, or a metabolic or toxic cause.

When initially examined, the patient was unconscious and unarousable; however, he quickly regained some level of consciousness. He had normal vital signs and did not require resuscitation or cardioversion — it seemed unlikely, then, that he had had a prolonged cardiac arrest and resultant cerebral ischemia leading to coma. A catastrophic neurologic event, such as intracerebral hemorrhage, should have been seen on the CT scan of the head, although early intracerebral bleeding or subtle subarachnoid hemorrhage remained a possibility. CT scanning will miss up to 7 percent of subarachnoid hemorrhages.
3 The toxicologic screening yielded no evidence of drugs that could cause coma, although he had been given diazepam. Finally, he had hit his head on falling, so that head trauma may have contributed to his loss of consciousness.

Syncope, defined as a transient loss of consciousness accompanied by loss of postural tone, is common and is a possible diagnosis in this case.4 Of the approximately 7800 men and women in the Framingham Heart Study,5 11 percent had reported a syncopal episode. Syncope accounts for 1 to 3 percent of visits to emergency departments and as much as 6 percent of hospital admissions.1,6

All forms of syncope result from a sudden decrease in cerebral blood flow — a low-flow state.7 A 35 percent reduction in cerebral blood flow, or a complete disruption of cerebral perfusion for 5 to 20 seconds, will result in depletion of the brain's oxygen stores and lead to syncope.8,9 In syncope, the resumption of cerebral blood flow is rapid; no neurologic sequelae occur. In contrast, in a prolonged no-flow state, as in cardiac arrest, brain glucose and adenosine triphosphate stores are depleted after five minutes and a cascade of chemical derangements ensues, leading to neuronal death and coma after the cardiac arrest. After 10 minutes without cerebral perfusion, meaningful neurologic recovery at normal body temperature is rare.9,10

This patient had a spontaneous resumption of blood pressure and cerebral perfusion in the 11 minutes after falling and before the arrival of the emergency medical service. When he was examined in the emergency department, he responded to noxious stimuli with withdrawal of all extremities and showed no evidence of a focal lesion in a cerebral hemisphere. His normal pupillary responses suggested preserved midbrain function. However, the fact that he did not open his eyes spontaneously or vocalize suggests a deeper level of unconsciousness than would be expected after syncope. Possible explanations include the effect of intravenous diazepam, the result of head trauma, or a postictal state.

In addition to a prolonged alteration in consciousness, this patient had flexor movement of his right arm. Seizure can lead to prolonged periods of confusion and is often confused with syncope. Conversely, involuntary movements (myoclonic jerks) may accompany cardiogenic syncope in approximately 20 percent of patients and frequently result in a misdiagnosis of seizure.11 Without simultaneous electroencephalographic and electrocardiographic recordings, differentiating seizure and syncope may be difficult. The precipitants of the episode, as well as premonitory or prodromal symptoms, may help the physician to distinguish between the two. Loss of consciousness precipitated by pain, exercise, micturition, defecation, or stress is probably due to syncope. Sweating and nausea before and during loss of consciousness are also more likely to occur with syncope than with seizure. An aura before the event and disorientation, persistent confusion, and delayed return of consciousness after the event are more frequent in seizure. Rhythmic movements can occur with both, but repeated tonic–clonic movement is characteristic of a seizure.

The findings in this patient overlap these categories. He was exercising before his loss of consciousness, which suggests syncope. He had a delay in his return to consciousness, more suggestive of a seizure. Arguing against a seizure is the lack of repeated tonic–clonic movement, as reported by the first responders. Furthermore, he did not have an anion gap reflective of a metabolic acidosis, which is often seen in seizure.12 The most likely diagnosis for this patient was syncope, with prolonged decrease of consciousness due to a combination of poor cerebral perfusion and subsequent medications.

Syncope can be divided into that due to neurogenic causes and that due to cardiogenic causes. Neurogenic syncope is more than twice as common as cardiogenic syncope.6,13 History, physical examination, laboratory tests, and the electrocardiogram are the cornerstones of an accurate diagnosis of the underlying cause (Table 2). The history and physical examination identify the cause in 45 percent of patients and result in directed testing that identifies the cause in another 8 percent. Laboratory abnormalities detected on routine testing identify the cause in 2 to 3 percent of patients, and the electrocardiogram provides clues to the cause of syncope in about 5 percent of cases.4

Vasovagal syncope is the most common cause of a transient loss of consciousness.
4,12 The vasodepressor component was first suggested by John Hunter in 1773, on the basis of his observation of a patient undergoing phlebotomy.14 The pathophysiology is not completely understood, and it is likely that both the triggers and the mechanisms are numerous.15 Although vasovagal syncope is usually gradual in onset, sudden loss of consciousness can occur. Tilt testing and medications such as isoproterenol or nitroglycerin can be used to provoke a vasovagal response and establish the diagnosis in patients with recurrent episodes.16 Vasovagal syncope does not appear to be associated with an appreciably increased risk of death.

Cardiac syncope, in contrast to vasovagal syncope, can be a harbinger of serious disease, with a five-year mortality approaching 50 percent.5,8 Arrhythmias are the most common cardiac cause of syncope, accounting for up to 14 percent of all cases of cardiogenic syncope.4,6,17 These include bradyarrhythmias from sinus-node dysfunction, atrioventricular conduction disorders, and tachyarrhythmias. Ventricular tachyarrhythmias may be due to structural heart disease (in 85 to 90 percent of cases), the long-QT syndrome, or the Brugada syndrome.6

Syncope during exercise, with no prodrome, as seen in the patient under discussion, suggests cardiogenic syncope. Ischemic disease is a possible cause, but the patient's relatively young age argues against it. Hypertrophic cardiomyopathy is an important consideration. This disease can range from being an asymptomatic condition to a cause of sudden death due to malignant ventricular arrhythmias.18 An electrocardiogram performed on a patient with this condition generally shows left ventricular hypertrophy, and when the apex of the heart is involved, it can show diffuse T-wave inversions across the precordium.19 Both of these changes were seen in the patient we are discussing. Finally, the history of previous sudden syncope during exercise led us to a diagnosis of syncope from a cardiac arrhythmia, resulting from hypertrophic cardiomyopathy. The diagnostic test was a transthoracic echocardiogram.

Dr. William D. Binder's Diagnosis

Syncope due to arrhythmia associated with hypertrophic cardiomyopathy.

Pathological Discussion

Dr. Mary Etta King: In the parasternal long-axis view and the short-axis view, the left ventricle appears to be hypertrophied. The septum is markedly more hypertrophic than the free wall (Figure 1; see also Video Clip 1 and Video Clip 2 of the Supplementary Appendix). The septum is 2.5 cm thick and the thickness of the free wall is about 1.5 cm; for both, the normal wall thickness is 0.7 to 1.1 cm. The left ventricular systolic function was excellent, with an ejection fraction of 82 percent. The aortic valve is anatomically and functionally normal, and there is no evidence of left ventricular outflow obstruction at any level. In a young person, abnormalities of the coronary arteries can be a cause of syncope. In this case, there was no evidence of anomalous origin of either of the coronary arteries.

From the apical long-axis view, the left ventricular outflow tract is shown with systolic anterior motion of the mitral chordal apparatus, but no hemodynamically significant dynamic outflow tract obstruction (Figure 2 and Video Clip 3, both in the
Supplementary Appendix). The study was repeated two days later to assess outflow tract obstruction further; at rest, the peak outflow tract gradient was 12 mm Hg, and with the Valsalva maneuver it was 15 mm Hg, indicating no provocable gradient across the outflow tract. In the apical four-chamber view, color Doppler examination showed mild mitral insufficiency (Video Clip 4 of the Supplementary Appendix).

In summary, the findings on this transthoracic echocardiogram are hypertrophic cardiomyopathy with asymmetric septal hypertrophy and normal systolic function, mild mitral regurgitation, and no dynamic outflow obstruction.

Dr. James R. Stone: The characteristic pathologic feature of hypertrophic cardiomyopathy is cardiac hypertrophy, which is typically, but not always, asymmetric, with disproportionate involvement of the ventricular septum (Figure 2A)20,21 in the absence of extrinsic causes of myocardial hypertrophy, such as hypertension. The enlarged ventricular septum may impinge on the left ventricular outflow tract, resulting in physiological subaortic stenosis, and also frequently makes contact with the anterior leaflet of the mitral valve, resulting in endocardial fibrosis of the left ventricular outflow tract (Figure 2B). The most specific histologic feature of hypertrophic cardiomyopathy is extensive disorganization of myocyte structure, which is called myocyte disarray (Figure 2C) and which is characterized by the presence of abnormally branched (Y-shaped) myocytes, with adjacent myocytes arranged perpendicularly or obliquely to one another.

Figure 2. The Heart of a 38-Year-Old Man Who Died from Hypertrophic Cardiomyopathy.

The posterior view of the sectioned heart (Panel A) shows abnormal thickening of the left ventricle (left side of image) with disproportionate involvement of the ventricular septum. The right ventricle is also hypertrophied, and both atria show dilation and contain mural thrombi. A magnification of the left ventricular outflow tract (Panel B), with the anterior leaflet of the mitral valve pulled away, reveals endocardial fibrosis of the outflow tract (arrow). A histologic section of the myocardium from the ventricular septum (Panel C, hematoxylin and eosin) shows myocyte disarray, interstitial fibrosis, and enlarged myocyte nuclei.

Myocyte disarray involving less than 5 percent of the myocytes is present in hearts with hypertrophy from diverse causes. Disarray involving more than 20 percent of myocytes is highly specific for hypertrophic cardiomyopathy. The mutated sarcomeric proteins that cause the disease are incorporated into the muscle and have a dominant negative effect through the alteration of contractility, energy metabolism, or both.
22,23,24 In animal models, myocyte disarray appears early in the course of the disease, and may represent a primary phenomenon due to incorporation of the mutated proteins into the cardiac sarcomeres.25,26 The myocyte hypertrophy and interstitial fibrosis are thought to be secondary changes that occur relatively late in the course of the disease in response to the elevated levels of growth factors such as angiotensin II.27,28

Discussion of Management

Dr. Michael A. Fifer: This patient has had two episodes of exertional syncope, with echocardiographic findings of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy29,30,31 is characterized by idiopathic hypertrophy of the left (and sometimes right) ventricle, heart failure due to diastolic dysfunction, ischemia even in the absence of coronary artery disease, and arrhythmias. Its prevalence is estimated at 0.2 percent, which means that there are approximately 600,000 affected persons in the United States. There are several variants. Hypertrophic obstructive cardiomyopathy (formerly and still occasionally termed idiopathic hypertrophic subaortic stenosis), in which there is asymmetric septal hypertrophy and a pressure gradient across the left ventricular outflow tract, is seen in 25 percent of cases. Other variants include asymmetric septal hypertrophy without obstruction, apical hypertrophic cardiomyopathy, midcavity obstruction, and concentric hypertrophy mimicking that caused by hypertension or valvular aortic stenosis. This patient had asymmetric septal hypertrophy without obstruction, the most common variant. The disease is often familial, with autosomal dominant inheritance; thus, when this patient awakened, a family history would be important. Approximately 200 mutations in 10 genes encoding sarcomeric proteins have been shown to cause hypertrophic cardiomyopathy.

The clinical manifestations of the disease are dyspnea, angina, and a continuum encompassing lightheadedness, presyncope, syncope, and sudden death. The presentation of this patient fell within this spectrum.32,33 The incidence of sudden death is approximately 1 percent per year.7,34,35 Syncope or sudden death may occur in previously asymptomatic patients, although the incidence is lower than in symptomatic patients.34 Symptoms often occur during physical exertion, as in this patient. Hypertrophic cardiomyopathy is the most common disease found in cases of sudden death in young athletes.36,37 It must be distinguished from what is called the "athletic heart syndrome," in which vigorous exercise is accompanied by physiologic left ventricular hypertrophy and electrocardiographic changes.38 Patients with hypertrophic obstructive cardiomyopathy are at risk for infective endocarditis.

Sudden death in hypertrophic cardiomyopathy generally results from ventricular tachycardia or fibrillation.32 Risk factors for sudden death are listed in Table 3. Cardiac arrest is unusual in patients who have no risk factors.40 This patient had had a previous episode of syncope and had marked left ventricular hypertrophy, two of the risk factors for sudden death.33,40

As in this patient's case, most patients with nonobstructive hypertrophic cardiomyopathy have no murmur, even during the Valsalva maneuver, because they have no resting or provocable left ventricular outflow tract gradient. Most patients have abnormal findings on electrocardiograms, however, including left ventricular hypertrophy, conduction defects, and pseudoinfarct patterns. This patient had both left ventricular hypertrophy with ST-segment and T-wave abnormalities (left ventricular strain) and abnormal intraventricular conduction. The abnormalities on his electrocardiogram provided an important clue to a cardiac cause of syncope.

The gold standard for the diagnosis is echocardiography, which confirmed the diagnosis of hypertrophic cardiomyopathy in this case. Magnetic resonance imaging may add value in patients with technically inadequate echocardiograms and in those with apical hypertrophic cardiomyopathy, which may be difficult to characterize by echocardiography. Cardiac catheterization is not necessary for diagnosis; its use is reserved largely for the detection of concurrent coronary artery disease. Genetic analysis is not yet routinely available, but it may be useful for diagnosis in borderline cases or when differentiation between hypertrophic cardiomyopathy and the athletic heart syndrome is necessary.

The management of hypertrophic cardiomyopathy has five components (Table 4). The screening of the patient's relatives should include echocardiography, beginning with any who are in the teenage years. Most competitive sports activities are prohibited41; the patient under discussion had been advised to refrain from playing soccer. The advisability of recreational, noncompetitive sports activities has been formally addressed in a recent American Heart Association Scientific Statement42: jogging is considered an "intermediate" activity "to be assessed clinically on an individual basis." Certainly, a patient such as this one would be advised not to jog. With any exercise, it is important to avoid volume depletion, which may induce or exacerbate outflow obstruction and cause hypotension.

The cornerstone of treatment for control of symptoms is beta-blockade therapy. In patients with hypertrophic obstructive cardiomyopathy, disopyramide, alone or in combination with another drug, may reduce the gradient and ameliorate symptoms. In patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to optimal medical therapy, septal myectomy
43 or alcohol septal ablation44 may be considered. For the prevention of sudden death, medical treatment with high-dose beta-blockade therapy or with amiodarone has been suggested but has not been demonstrated to reduce the risk of this catastrophic event. Survivors of cardiac arrest are generally treated with the implantation of a cardioverter–defibrillator. When cardioverter–defibrillators are implanted for secondary prevention, they fire appropriately to terminate ventricular tachycardia or fibrillation at the rate of 11 to 17 percent per year.32,45 When they are implanted for primary prevention in patients with one or two risk factors for sudden death who have not had cardiac arrest, they fire appropriately at the rate of 5 to 10 percent per year.32,45 Cardioverter–defibrillator implantation would be appropriate for a patient such as this with recurrent syncope and marked left ventricular hypertrophy.

A medical student: Are black people at high risk for hypertrophic cardiomyopathy?

Dr. Fifer: Maron et al.46 reported that black Americans are overrepresented among athletes with sudden death who are found at autopsy to have hypertrophic cardiomyopathy, but they are underrepresented among patients with the antemortem diagnosis of hypertrophic cardiomyopathy.

Dr. Nancy Lee Harris (Pathology): Dr. Binder, how was the patient treated?

Dr. Binder: Treatment with metoprolol was begun in the emergency department and a cardiac monitor was placed. He regained consciousness as the sedation wore off and was admitted to the hospital. After he was extubated, he reported that his mother had a "thickened heart," but that there was no history of sudden death in his family. He had had an episode of asymptomatic bigeminy on the night of the day he was admitted. On the third hospital day, a single-chamber implantable cardioverter–defibrillator was placed. He was discharged on the seventh hospital day with instructions to take aspirin, atenolol (75 mg daily), and diazepam as needed for vertigo, and to follow up with a cardiologist at another hospital.

Dr. Harris: Dr. Das, I believe you have seen the patient recently.

Dr. Saumya Das (Cardiology): Six months and again one year after discharge, the patient had syncope, the first time while jogging (having been told after a stress test that he could resume jogging) and the second time while walking uphill. Each time the defibrillator recorded ventricular tachycardia, appropriate firing of the device, and return to sinus rhythm. He had been taking metoprolol, 50 mg daily; after the first episode, the dose was increased to 100 mg daily. During the most recent admission, his medication was changed to sotalol, 120 mg twice daily, and he was instructed to walk slowly and to avoid hills while walking, if possible. If he continues to have arrhythmias, we will consider attempting radiofrequency ablation of the focus of ventricular tachycardia. His children have been screened and do not have signs of hypertrophic cardiomyopathy.

Anatomical Diagnosis

Hypertrophic cardiomyopathy.


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