A 37-year-old woman was referred to Hermann Hospital from a local health maintenance organization clinic for the evaluation of fatigue, chest pain, and syncope.
The patient was in her normal state of health until approximately 6 months before admission, when she began suffering mild fatigue. Her fatigue initially consisted of effort intolerance. She reported having an increased amount of breathlessness when climbing the flight of stairs to her second-floor apartment. Approximately 4 months before her hospital admission, she had the first of four syncopal episodes. The first episode occurred as she proceeded to walk after a long period of standing. At that time, she sensed the onset of chest tightness and dizziness before losing consciousness.
She did not initially seek medical attention for her fatigue and syncope. She reported having dizzy spells that were initially associated with chest tightness and mild breathlessness. Her dizzy spells, which initially occurred weekly, became more frequent such that they occurred daily during the month before her hospital admission. Her chest discomfort was described as a squeezing sensation that was substernal in location without radiation to any other position. It was usually associated with dizziness and breathlessness but never with nausea, vomiting, or diaphoresis. Her chest discomfort occurred at rest and with exertion.
The three syncopal episodes that followed the first occurred approximately 1 month apart. Each of these episodes occurred as she proceeded to stand and walk from a sitting or lying position. Her syncope was always preceded by substernal chest pressure, dizziness, and breathlessness.
The patient is employed as a school bus driver. She reported having symptoms of dizziness and near syncope frequently while driving the bus. There was a history of smoking for approximately 10 years, averaging a pack of cigarettes per day. There was no history of fever, illicit drugs, alcohol, receipt of blood products, recent travel, or exposure to toxic chemicals. There was no medical history of seizure disorder, diabetes, or hypertension. There was a report of a strong family history of coronary artery disease. Her father and paternal aunt suffered myocardial infarctions in their fifties, and a brother died secondary to a myocardial infarction at the age of 37 years.
Vital signs were: temperature, 99.0° (oral); blood pressure, 118/78 mm Hg; pulse, 78 (no orthostatis changes); and respiratory rate, 16 per minute (unlabored). The patient was a well-developed woman who appeared to be her stated age. She was in no apparent distress. HEENT was normal except for right fundi with a small pale lesion at the 10 o’clock position. The neck showed no jugular venous distension and showed normal carotid upstrokes without bruits or murmur. Normal bronchovesicular breath sounds were heard throughout the lung fields. The heart rate was normal with a regular rhythm. A prominent first heart sound was heard throughout the precordium. A late diastolic sound was heard at the apex position. A grade 1 systolic murmur was intermittently heard at the apex position. The abdomen was soft, with no organomegaly and with normal bowel sounds. Pulses were normal. External was warm; no skin rash, splinter hemorrhages, clubbing, or cyanosis was found. Neurological examination was completely normal.
Laboratory values were Na, 138; K, 4.3; Cl, 104; CO2, 32; BUN, 12; CRT, 1.2; Glu, 103; Mg, 1.7; Ca, 9.0; WBC, 6.6; Hgb, 12.5; Hct, 38.0; MCV, 92; PLT, 269; ESR, 7 MM/HR; urinalysis, WNL; and liver function, WNL.
The ECG is shown in Fig 1⇓. The chest radiograph showed normal heart size and pulmonary vasculature with no infiltrates. The patient was admitted to the hospital and underwent diagnostic procedures.
Albert E. Raizner, MD
There are a variety of ways to approach this case of a young woman, previously in good health, who presents with a 6-month history of fatigue, shortness of breath, and then more specific symptomatology, namely episodes of syncope. She not only had four overt syncopal episodes but experienced multiple episodes of dizziness as well. Perhaps most important, these episodes tended to occur when she was in an upright position and while walking, so it was a positional syncope.
If we approach the differential diagnosis from the perspective of disease types that cause syncope (Table 1⇓), we can hone in on the pertinent features of the case.1 First, a common cause of syncope is impaired or inappropriate autonomic function. This is especially common in younger people and is one of the first things to consider. Second, cardiac causes of syncope are also common and point to specific hemodynamic or rhythm problems. Third are those that fall into the category of seizures or psychogenic causes. A fourth category of syncope may be termed mechanical syncope, in which a physical maneuver interferes with blood flow into or out of the heart.
In the category of impaired or inappropriate autonomic function, patients with orthostatic hypotension are commonly found. This patient with syncope and dizziness most often in an upright posture could fall into that category. In many patients with orthostatic hypotension, a primary cause is never found.2 This entity may be called idiopathic orthostatic hypotension. There is another small group that has disease in the corticospinal tracts, extrapyramidal or cerebellar, called the Shy-Drager syndrome. There are many secondary causes of orthostatic hypotension. Orthostatic hypotension may be related to drugs. Most drugs used for treating heart disease or hypertension are capable of lowering the blood pressure or impairing the ability of the body to react to changing positions. This is perhaps the most common cause of orthostatic hypotension seen in medical practice. Diabetes is also a common cause of orthostasis. The elderly have less compliant blood vessels and do not respond as well as younger individuals to changes of position. They tend to be more sensitive to medications that cause further impairment of blood vessel or neurogenic reactivity. There are many other causes of orthostatic hypotension as well.
Vasodepressor or vasovagal syncope is a phenomenon reflecting inappropriate autonomic responsiveness. In light of the circumstances in which it often occurs, it has been termed situational syncope. Carotid sinus hypersensitivity is an uncommon but very important cause of syncope.3 A characteristic clinical feature would be lightheadedness when shaving or when turning the head.
Of the cardiac causes, some involve hemodynamic disorders and some involve arrhythmias. Of those that involve hemodynamic problems, there generally has to be some form of obstruction. Left heart problems include stenotic valve lesions (aortic stenosis, mitral stenosis), hypertrophic cardiomyopathy, and tumors, the prototype of which is the myxoma (left atrial myxoma). Right heart problems include pulmonic stenosis, pulmonary hypertension, pulmonary emboli, and right atrial myxomas.
Arrhythmias are a frequent cause of syncope and may take the form of bradyarrhythmias and tachyarrhythmias.4 Bradyarrhythmias are more common in older individuals who may have a sick sinus syndrome or types of high-grade atrioventricular (AV) block. Bradyarrhythmias may be drug induced. β-Blockers, digoxin, and some calcium channel blockers are common culprits in this regard, particularly if there is some underlying intrinsic disease of the sinus node or AV node. Of the tachyarrhythmias, ventricular tachycardia and ventricular fibrillation are serious causes of syncope that are usually but not always associated with underlying heart disease.5 Supraventricular tachycardia is much more common but does not often cause syncope unless the rate is extremely rapid (more than 220 beats per minute) or it is associated with other types of heart disease.
Syncope may be due to seizures and psychogenic causes. Grand mal seizures are usually not difficult to diagnose because of the tonic-clonic movements and the postictal stupor. More subtle are the complex partial seizures, which may present simply as syncope or lightheadedness with no premonitory findings and not many other clinical features to go by. Panic disorders are very common and must be considered in a young individual who has other symptoms that may be anxiety related, such as fatigue, shortness of breath, and chest pain.6 Patients with panic disorders may pass out as abruptly as someone who has an Adams-Stokes attack from complete heart block.
In the category of mechanical syncope are cough syncope and defecation syncope.7 These are essentially exaggerated Valsalva maneuvers. Cough syncope is often associated with additional underlying lung disease and/or pulmonary hypertension. Micturition syncope is not purely mechanical because there are autonomic disturbances associated with it.8
Now, let’s look at our patient’s specific clinical features to see if we can narrow down the causes and focus on what this patient might have.
First, and perhaps most important, is the positional nature of this patient’s syncope. Many of the episodes of true syncope occurred when she stood up and walked. Autonomic dysfunction, orthostatic hypotension, and some of the cardiac hemodynamic causes are classic causes of positional syncope. Arrhythmias tend to occur at any and odd times, and it would be a little unusual for an arrhythmia to be the cause of purely positional syncope. Seizures, of course, are not positional. Mechanical causes may be positional, but those positions are not described in this case.
The patient’s symptoms of shortness of breath and chest pain are important indicators. Shortness of breath and chest discomfort are consistent features in most of the cardiac hemodynamic causes of syncope. They can also be associated with arrhythmias, autonomic disturbances, and with some of the psychogenic causes of syncope.
The physical examination in this patient provides some important clues. The fact that she had no orthostatic blood pressure change mitigates against but does not eliminate the possibility of orthostatic hypotension or autonomic dysfunction. Some patients require being upright for several minutes before they manifest their orthostatic change. If orthostasis in this patient was tested in the usual but incorrect manner in which we lie a patient down, then stand them up and immediately record the blood pressure, we may fail to detect orthostatic hypotension. The proper way to measure orthostatic blood pressure change is to have the patient stand up, allow them several minutes to develop symptoms, and then measure the blood pressure.
The fact that there is a lesion in the fundus may be a red herring but suggests some embolic phenomenon from the heart and points to one of the cardiac causes. A prominent first heart sound is an important abnormal cardiac finding, although it is not specific. The late diastolic sound is not described in detail. I am presuming it to be presystolic, analogous to a fourth heart sound. This, too, is not a normal finding in a 37-year-old woman, so the prominent first heart sound and late diastolic sound each point to a cardiac cause. The intermittent systolic murmur, if real, further directs our attention to a cardiac hemodynamic cause of this patient’s syncope.
Let’s look more closely at the specific cardiac hemodynamic left heart and right heart problems that may cause syncope. The left heart problems include aortic stenosis9 and mitral stenosis, examples of fixed obstruction, and hypertrophic cardiomyopathy10 and left atrial myxoma,11 examples of dynamic obstruction. The right heart cardiac problems include pulmonic stenosis, pulmonary hypertension, pulmonary embolus, and right atrial myxoma.
All of these problems except for pulmonary embolus tend to be positional. Any cardiac disease that impairs flow through the heart will be sensitive to the volume of blood returning to the heart. Upon standing, there is a decrease in venous return compensated by increasing heart rate and vasoconstriction, but patients with fixed or dynamic obstruction may not adequately compensate for positional change. Pulmonary embolus, however, is not a typical cause of positional syncope unless there is pulmonary hypertension, so we can eliminate it from consideration.
The patient’s shortness of breath initially was one of her principal complaints until it became dominated by the more dramatic symptom of syncope. Diseases of the left heart cause shortness of breath by elevation of left atrial and pulmonary capillary wedge pressures, particularly during effort. On the other hand, right atrial myxoma is not likely to cause shortness of breath, so we will eliminate it from consideration.
This patient not only had some pertinent abnormal findings but had some pertinent normal findings that are equally important. She had a normal second heart sound. Pulmonary hypertension and pulmonary embolism should accentuate the pulmonic component of the second heart sound, whereas pulmonic stenosis should diminish it. Therefore, the finding of a normal second heart sound will help to eliminate the right heart causes of syncope. Furthermore, the ECG, despite the rightward axis, had no other features of right ventricular or atrial hypertrophy or strain. It is not abnormal for a young individual, particularly with a thin, asthenic physique, to have a rightward axis. Thus, the absence of any evidence of right atrial enlargement or right ventricular hypertrophy is strong evidence against these right heart pathologies. The normal chest radiograph would also be unusual for a patient with pulmonic stenosis, who should have a dilated poststenotic pulmonary artery or pulmonary hypertension, which should show abnormal lung vascular findings. These features combined eliminate the right heart disorders from consideration.
Let’s focus on the left heart pathology. The absence of a persistent systolic murmur would be virtually unheard of in a patient with aortic stenosis. Furthermore, a normal carotid upstroke would certainly mitigate against this being aortic stenosis.
A loud first heart sound may be heard in several situations. These include vigorous left ventricular contraction, as in some patients with hypertrophic cardiomyopathy, a short PR interval, which this patient does not have, and high left atrial pressure at the time of mitral valve opening, as might occur in patients with mitral stenosis and atrial myxoma.12 So we are left to choose between mitral stenosis, hypertrophic cardiomyopathy, and left atrial myxoma.
Late diastolic sounds can be heard in each of these conditions. However, the absence of an early diastolic sound or opening snap is unusual in mitral stenosis if the valve is still pliable. In addition, we ought to hear an early diastolic rumble, which this patient did not have. Finally the absence of ECG evidence of left atrial enlargement should eliminate mitral stenosis from serious consideration.
We are left with serious diagnostic considerations of hypertrophic cardiomyopathy13 or left atrial myxoma.14 15 They are both causes of dynamic obstruction. The former represents a form of dynamic outflow obstruction and the latter represents dynamic inflow obstruction, but because they are dynamic and vary with position and with flow volume, the murmurs associated with these entities can be intermittent, a finding described in our patient. Yet, most people with hypertrophic cardiomyopathy also have left ventricular hypertrophy, which this patient does not have, at least by ECG. The absence of left ventricular hypertrophy directs us away from hypertrophic cardiomyopathy and toward left atrial myxoma. When we come back to the subtle finding that was presented in the physical examination (the spot in the fundus), the possibility that this represents an embolic event leads us further to a left atrial myxoma as our diagnosis.16 Left atrial myxomas often are friable, and embolize, and, in fact, embolization is not an uncommon presentation, occurring in 25% to 30% of such patients.
No feature of this case is specific of a left atrial myxoma as opposed to other left atrial tumor types.14 17 Such differentiation requires tissue analysis. Since myxoma is the most common primary tumor in the left atrium, my final clinical diagnosis is left atrial myxoma.
Kent A. Heck, MD, Assistant Professor of Pathology and Laboratory Medicine
A specimen labeled “mitral valve tumor,” which consisted of several fragments of soft, rubbery tissue, was received in surgical pathology. Each of the fragments had multiple tan fronds projecting from a single pink stalk. On histological examination, each of the fronds was covered by a single layer of endocardial cells. Below these cells resided a layer of loose connective tissue with poor cellularity surrounding a densely collagenous fibrovascular core. Movat’s stain confirmed the presence of elastic tissue within and surrounding these central cores. No thrombi were adherent to the tumor. These histological features are characteristic of a papillary fibroelastoma (Figs 2⇓ and 3⇓).
Only 7.9% of primary cardiac tumors are papillary fibroelastomas (PFEs).18 PFEs are the most common primary cardiac valvular tumor and comprise approximately 73% of this subset of tumors.19 PFEs most commonly arise from the aortic valve but may be nonvalvular in a minority of cases. The tumor stalk is usually attached to the free edge or the midportion of the valve and may rarely involve several different valves.
The location of valvular tumors may be predictive of clinical manifestations. According to Edwards et al,20 mitral valve tumors are much more likely than aortic valve tumors to produce serious neurological symptoms or sudden cardiac death. Although PFE is often an incidental finding at the time of autopsy, the tumor may be discovered as a result of clinical manifestations. Syncope is not associated with this tumor type, but seizures secondary to embolic stroke have been reported in several cases.19 Mitral valvular location may rarely be associated with sudden cardiac death, angina pectoris, transient ischemic attack, and embolic stroke.18 19 20 21 The latter is presumably secondary to formation of fibrin thrombi along the tumor papillae.19 Embolic material composed of tumor fragments has been postulated as a potential source, but this is not clearly documented.
Long-term clinical follow-up is not well documented for this tumor. Some reports suggest that recurrence is unexpected after complete tumor resection.22
The final diagnoses were papillary fibroelastoma arising from the mitral valve and neurocardiogenic syncope. The relationship of these two entities in this patient is uncertain. (Table 2⇓).
- Copyright © 1995 by American Heart Association
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