Syncope

FOREWORD This discussion of syncope is one of the best that I remember having read. It is a logical and practical one, particularly to the practicing physician. It enables one to “sink the teeth” into the important pertinent aspects of diagnosis and management of this problem. Syncope generally connotes an abnormality of either the cardiovascular or cerebrovascular systems. However, as pointed out by the authors, syncope (defined as nontraumatic loss of consciousness) is found in 6%-20% of presumably healthy individuals. It is therefore apparent that it occurs much more commonly than generally realized. Syncope and/or dizziness can be a frightening experience to our patients, the cause of which needs analysis and treatment including prevention, if possible. This discussion can serve as a special desk reference which can be reviewed to refresh one’s memory when encountering this problem in our patients, now as well as in the future.

W.

PROCTORHARVEY, M.D. EDITOR-IN-CHIEF

SELF-ASSESSMENT

QUESTIONS

1. The incidence of syncope, defined as nontraumatic loss of consciousness, is a. Less than 5% ofthe general population. b. 6%-20% ofpresumably healthy individuals. c. More than 20%. d. Unknown. 2. The sick sinus syndrome is characterized by: a. Persistent and unexplained sinus bradycardia. b. Periods of sinus arrest with or without the appearance of a rescuingjunctional pacemaker. c. Periods of supraventricular tachycardia, atria1 fibrillation, or flutter, frequently with a slow ventricular response. d. Episodes ofsinoatrial exit block. e. All ofthe above. 3. Regarding the workup of patients with syncope, select the correct statement: a. An etiologic diagnosis can be established in all patients studied. b. Electrophysiologic studies are always indicated in patients with unexplained syncope. c. A syncopalepisodethatremains unexplained after extensive workup is likely not to recur during the following 2 years. a cardiac cause can be estabd. After extensive workup, lished for most ofthe syncopal episodes studied. e. All ofthe above. 4. Regarding patients with "high-risk" bundle-branch block (left bundle-branch block, right bundle-branch block with left anterior or left posterior hemiblock) select the correct statement: a. Progression to complete heart block has never been documented. b. Progression to complete heart block occurs in more than 10% of the patients. c. Progression to complete heart block is more likely when the HV interval islongerthan 60 msec. d. Syncope in these patients is a sign ofprogression to cornplete heart block and a risk factor for sudden death. e. None of the above. 5. Regarding the sick sinus syndrome, select the correct statement:

a.

The abnormality is confinedtothe sinus node in the majority of patients. b. Bradycardia and tachycardia seldom occur in the same patient. c. The incidence of syncope is more than 80% in patients with the brady-tachy syndrome. d. In sinus node exit block, some P waves are not followed by a QRS complex on the ECG. e. None ofthe above. 6. In patients with asymmetric septal hypertrophy (ASII): a. Syncope is present in less than one third ofpatients. b. Left ventricular outflow obstruction is probably the most frequent cause ofsyncope. c. Propranololtherapy is usually effective in controlling the arrhythmias. d. Aggressive antiarrhythmic therapy when appropriate (in addition to propranolol) may reduce significantly the incidence ofsyncope and sudden death. 7. Regarding orthostatic hypotension due to autonomic insufficiency, select the correct statement: a. It can be differentiated from hypotension due to volume depletion by the absence of a tachycardic response to standing. b. It is frequently accompanied by impotence and urinary bladder or bowel dysfunction, especially in severe cases. c. An absence ofthe hypertensive overshoot after cessation offorced expiration (Valsalva maneuver)is characteristic ofthis syndrome. d. Symptomatictreatmentwhen no reversible causes can be found is frequently unsuccessful. e. All ofthe above. 8. Match the drug with the mechanism ofsyncope (more than one mechanism can be matched with each group ofdrugs): 1. AV block a. Diuretics and antihypertensives b. Digitalis 2. Orthostatic hypetension tachc. Class I antiarrhythmics 3. Ventricular yarrhythmias d. Tricyclic antidepressants 4. Left ventricular outflow obstruction in certain patients e. Phenothiazines 9. Regarding carotid sinus hypersensitivity, select the correct statement: a. Atropine corrects both the vasodepressor and the cardioinhibitory response to carotid sinus stimulation. b. Carotid sinus hypersensitivity is said to exist when ca5

10.

11.

12.

rotid sinus massage induces sinus pauses of 1 second or longer. c. Carotid sinus hypersensitivity is said to exist when carotid sinus massage induces a fall in blood pressure of more than 10 mm Hg. d. The coexistence ofcarotid sinus hypersensitivity and sick sinus syndrome in the same patient is seen in less than 10% of patients studied. e. None ofthe above. Regarding patients with ischemic heart disease, select the correct statement: a. Syncope is found to be related to the occurrence of ventriculartachyarrhythmias in more than 30% ofpatients. b. Ischemic heart disease is found in more than 30% ofpatients with syncope of unknown etiology. c. The left ventricular ejection fraction is more useful than the presence of arrhythmias to detect patients at risk of sudden death. d. More than 50% ofpatients with the sick sinus syndrome are found to have coronary artery disease. e. Allofthe above. Regarding the detection of arrhythmias on Holter monitoring, select the correct statement: a. Major arrhythmias are recorded in the absence ofsymptoms in more than 80% of cases. b. Less than 10% ofthe patients with ventriculartachycardia experience symptoms concurrently with the arrhythmia. c. Of all patients with nonsustained ventricular tachycardia, only those with a history of congestive heart failure or congestive cardiomyopathy are at high risk of sudden death. d. The spontaneous day-to-day variation ofectopy frequency is more than 20%. e. All ofthe above. Regarding electrophysiologic studies in patients with syncope, indicate which ofthe following statements is false: a. They are only indicated when the syncope is recurrent and no etiology can be found by noninvasive testing. b. They may yield an etiologic diagnosis in more than 50% ofpatients with recurrent syncope ofunknown etiology. c. A greatly prolonged HV interval in patients with bifascicular block is by itselfa strong indication that syncope is secondary to progression of the conduction disease to complete AV block. d. Electrophysiologic studies are less specific than Holter monitoring to confirm the cause ofsyncope. L'. None of the above-

13.

i-i.

In which of the following situations would you indicate the immediate insertion of a permanent pacemaker? a. A patient who on the second day after an acute myocardial infarction develops symptomatic second-degree AV block type I. b. A patient with chronic stableischemic heart disease with first degree AV block. c. A patient with no previous history of heart disease who has episodes of sinus bradycardia of less than 48 beats per minute and episodes ofsinus arrest lasting 2 seconds. d. A patient with bifascicular AV block and a prolonged HV interval of60 msec. stable ischemic heart disease, e. A patient with chronic symptomatic second-degree AV block type Mobitz II, and wide QRS complexes. 17. Allofthe above. A "pacemaker syndrome" consists of: a. Decreased cardiac output secondary to the loss of atria1 contribution during ventricular pacing. b. Decreased cardiac output due to mitral and tricuspid regurgitation during ventricular pacing and intact VA conduction. c. Symptoms of systemic and pulmonary congestion due to mitral and tricuspid regurgitation during ventricular pacing and intact VA conduction. d. Closed-loop tachycardias produced by certain dual-mode pacemakers. e. Allofthe above.

Answers

are

listed

at the

end

of the

article.

ROBERTO

P.

MEDINA received

his M.D. degree from the National University of Aires, Argentina, in 1977. He completed an internship and residency training in Internal Medicine at Graduate Hospital in Philadelphia, Pennsylvania, and is currently a Cardiology Fellow at Lankenau Hospital,, Philadelphia. Dr. Medina is an Affiliate in Training of the American College of Cardiology.

Buenos

LEONARD

S.

DREIFUS received his M.D. degree from Hahnemann Medical College, Philadelphia, in 1951 and completed an internship and residency in Internal Medicine at Philadelphia General Hospital. Currently he is Research Associate Professor of Physiology and Biophysics, Hahnemann Medical College, and Chief, Cardiovascular Division, the Lankenau Hospital, Philadelphia.

SYNCOPE is generally defined as a sudden and transient loss of consciousness resulting from an impairment in cerebral metabolism, which inturnisthe consequence ofa briefdeprivation Generally, syncopal attacks may ofessential energy substrates.' be classified by duration into three types: (1) slight, usually describedby patients as dizzy spells, giddiness, or lightheadedness; (2) medium, characterized by a loss of consciousness for a few seconds and commonly referred to as "drop attacks"; and (3) severe,which may progress to convulsive seizuresthatusually occur when the cerebral anoxia persists for more than lo-15 seconds." Although the first type is not classified as syncope for statistical purposes, since no loss of consciousness is involved, the pathophysiologic processes leading to it are similar to those producing true syncopal episodes. Transient loss ofconsciousnessis a common occurrence in the general population. Its incidence varies from less than 1% to more

than

20%,

according

to

the

population

studied.

Of

approx-

imately 3,000 young (average age, 29.1 years) Air Force personnel questioned, 7% reported at least one episode ofnontraumatic transient loss of consciousness.' The incidence in the elderly population

is probably

higher.

The diagnostic workup ofpatients with syncope is frequently complex. In a recent study of108 patients admitted to an intensive care unit with syncope for diagnostic studies,47% were still undiagnosed at discharge and were classified as having '
to

the

etiology.

The

1-vear

mortality

for

patients

with

syncope of noncardiovascular or unknown cause in that study was about 6%, whereas it was 18.5% for patients with syncope of cardiovascular etiology. Furthermore, the syncopal episode prompting admission was an isolated one in 83% ofthe patients with unexplained or noncardiovascular syncope, who had no recurrent episodes at the end of2.5 years offollow-up.4 The data acquired on different diagnostic procedures during the evalution ofpatients with syncope are frequently conflicting and of questionable significance. In every case a firm temporal relationship must be established between such data and the symptoms ofthe patient studied before expensive and frequently risky therapeutic interventions, such as pacemaker implantation, are undertaken. The importance of such a correlation becomes more evident as sophisticated diagnostic tools are introduced. It is also known that asymptomatic persons commonly have abnormal findings when different imaging or monitoring devices are used. The significance of abnormal findings in this population is frequently unknown. In this monograph we discuss the problems encounteredinthe evaluation of patients with syncope, emphasizing the rational use of the many sophisticated diagnostic methods and devices available to the clinician. We take a step-wise approach to the workup of the patient with syncope and discuss the major modalities of therapeutic interventions in each category. We begin with a somewhat detailed discussion ofthe different physiologic mechanisms leading to syncope, which is necessary for a rational diagnostic workup and therapeutic strategy. This is followed by a discussion of the clinical settings in which syncope occurs, focusing on the different cardiovascular events that may lead to transient loss ofconsciousness. PHYSIOLOGIC

MECHANISMS

LEADING

TO

SYNCOPE

The deprivation ofenergy substratestothe brain, resulting in transient loss ofconsciousness, may develop at any ofthe following four levels: (1)intrinsictothe cerebral circulation; (2) at the level ofthe heart, as a result of a transient decrease in cardiac output; (3) as a resultofadecreasein arterialpressureto a level less than thatrequiredto perfuse the brain; or 14) as a result of a shortage of the required energy substrates as constituents of the blood delivered to the brain.

Although detail the considered epec1all.y

it is beyond the scope of this review to discuss in mechanisms ofcerebrovascular disease, they must be since the incidence ofcerebrovascular disease is high, in the elderly popla1ation 9

Syncope seldom results from cerebrovascular disease unless the anatomical process is particularly extensive. More commonly some other mechanism of diminished perfusion is superimposed on occlusive cerebrovascular disease to result in fainting. Therefore, slight cardiovascular abnormalities that might remain undetected in an otherwise healthy individual could result in syncope in a person with preexisting cerebrovascular dis, ease. In persons with cerebral arteriosclerosis, the cerebrovas-, cular resistance is increased and the cerebral blood flow Moreover, the rigid vessels are approaches a precarious state. unable to adjust to variationsinthe arterial pressure andtothe temporarily increased demand of other viscera for a greater share ofthe cardiac output. Thisleadsto atransientdecreasein cerebral blood ffow and subsequent syncopal attacks. Occasionally decreased cerebral perfusion results from disease in vessels An example of decreased other than those supplying the brain. cerebralperfusionisthe subclavian steal syndrome, produced by occlusive disease of the subclavian vessels and typically characterized by fainting with arm exercise. The mechanism is a shunting of blood past the brain via the circle of Willis to the vertebral artery andthencetothe subclavian artery distaltothe obstruction in order to provide bloodtothe exercising extremity. Although dramatic, this is an uncommon cause ofsyncope. Occasionally syncope results from a disequilibrium between the perfusion pressure of the brain and the intracranial pressure, even without intrinsic disease of the blood vessels supplyingthe CNS. An example ofthis mechanism is the so-calledtussive syncope. Persons with tussive syncope are usually heavy smokers with obstructive lung disease. The mechanism leading to syncope during paroxysms of coughing in these persons is a sudden increase in the intrathoracic pressure leading to a subsequent increase in the intracranial pressure, resulting in a decreaseinthe net perfusion pressure ofthe brain. Syncope occurs as a result of the sudden and transient cerebral ischemia." A tracheostomy performed for patients in whom tussive syncope results in incapacitating disease is very effective in preventing the syncopalepisodes (evenifthe paroxysms ofcough persist)by relievingtheincreased intrathoracic pressure occurring with the tussive episodes. W.P. years. tussive ingthis

HARVEY: I had a brother, a heavy I tried unsuccessfully to have him syncope occurring in a restaurantthathe he became an "evangelist" against

Micturition syncope may addition to vagal influences bladder. 10

result elicited

from by

cigarette smoker for many stop; it was only after his quit smoking. Followthe evils of smoking.

a similar distention

mechanism in ofthe urinary

W.P. HARVEY: In addition, probably contributing to micturition syncope is the fact that the individual, still sleepy, goes to the bathroom to urinate. A man’s blood pressure is likely lower than during waking hours, and while he is standing, he may strain with the act of urination. Since women are sitting when urinating, I would think this to be mainly a problem for males, but I do not know any statistics on this.

Occasionally, carotid sinus pressure exerted on one of the carotid arteries will result in syncope without any other negative chronotropic or vasodepressor effects. Head position may be an importantfactorin eliciting this type ofsyncope, as a turning of the head to one side can cause carotid artery buckling, with resultant inadequate cerebral blood flow. In summary, a reduction ofcerebral blood flow resulting from a plaque or clot or from the erosion of an ulcerative plaque in the vessels supplying the brain is an infrequent cause ofisolated syncope. When it does occur, the protracted loss ofconsciousness and the presence offocalneurologic signs in the unconscious patient will point to cerebrovascular disease as the cause. It is much more common for syncope to result from some minor form of one or more of the causes that we will subsequently discuss, especially in patients with preexisting silent cerebrovascular disease. Hence, the etiology may not be clearly identified from either the cardiovascular or neurologic standpoint, and in these cases management becomes more complex. Furthermore, combined phenomena such as underlying cerebrovascular occlusive disease associated with a moderate degree ofpostural hypotension or a minor disturbance ofcardiacimpulse formation or conduction may produce major symptoms: with few exceptions the systemic arterial pressure virtually mirrors the intracranial pressure, and when the former falls below 15 mm Hg or less of the latter for a few seconds, syncope may result. The arterial pressure obviously depends directly on the cardiac output and the total peripheral resistance; to reach a syncopal level, either cardiac output or peripheral resistance must decrease below a certain critical point or both must decrease simultaneously. DECREASED

CARCTAC

O~JTPTJT

The cardiac output is function of the stroke volume and the heart rate, but these two variables cannot be considered separately since they are, to a certain extent, interdependent. For example, slowing of the heart prolongs the ventricular filling period and engenders ventricular dilation, which by the FrankStarling mechanism produces an increase in stroke volume so that minute cardiac output may remain normal despite marked slowing of the heart rate. Consequently, bradycardia by itself may not significantly compromise the cardiac output: itcanbe a ?7

manifestation of normal physiology in a healthy heart as well as a protective mechanism in the presence of cardiac disease." Nevertheless, ifthe heart rate falls below certain values, a compensatoryincrease in stroke volume will no longer be enough to keep the cardiac output within acceptable levels, and cerebral anoxia and syncope may result. On the other hand, faster heart rates increase the cardiac output up to certain limits beyond which an even faster heart rate would significantly decrease the diastolic filling, which in turn would result in a decrease of stroke volume. The end result is that beyond certain limits, tachycardia may also result in decreased cardiac output with compromise of the cerebral circulation and syncope. The third mechanism ofcirculatory failure in this setting is a primary decrease ofthe stroke volume which may result from a compromise in the inotropic state ofthe heart, impairmentofthe free flow of blood during the filling period into the left ventricle as a result of obstruction or decreased compliance, or impairment of the outflow of blood from the left ventricle to the great vessels as a result of fixed or dynamic obstruction. The latter two mechanisms are much more frequent as the cause of syncope than a decreased inotropic state of the myocardium, since the alterations of consciousness resulting from acute or chronic heartfailure are usually not transient and so do not result in syncope. Therefore, we will analyze with some detail the alterations in heart rate (bradycardia and tachycardia), following with a discussion ofthe mechanism that may cause syncope by an alteration ofthe free flow of blood into the heart (inflow obstruction), or from the left ventricle to the great vessels (outflow obstruction). B radycardia

Although the physiopathologic mechanism by whichtachycardia or bradycardia may cause syncope are quite different, these two alterations of the chronotropic state of the heart must be considered together since they often constitute different aspects of the same pathologic process, the so-called brady-tachy syndrome. Curiously,bradycardia oflessthan 30 pulses per minute appears to be bettertoleratedthantachycardia ofmorethan 150 pulses per minute, with respect to both precordial discomfort and circulatory disturbances. On the other hand, the sudden severe reduction in forward blood flow associated with severe bradycardia frequently results in immediate cerebral manifestaCons6 Neurologic symptoms engendered by bradycardia, including syncope, dizziness, and/or memory lapse, can be incapacitating and result in serious injury or death, especially in individuals operating motor vehicles, dangerous machinery, or aircraft or working in potentially hazardous environments. Furthermore, 72

disability, accident, or death occurring in a person with known periods of bradycardia could leave the physician open to medicolegal consequences, even ifthe entire event was unrelated to a rhythm or rate disturbance. Episodes ofsyncope, with or without convulsive seizures, due to severe bradycardia of less than 20 pulses per minute or prolonged asystole (5-10 seconds or more) are often referred to as either Stokes-Adams episodes or, more correctly, the MorgagniStokes-Adams syndrome. These early clinicians first pointed out that syncope was accompanied by a heart ratethatwas usually slow between attacks and even slower or absent during attacks.7 But bradycardia is not necessarily a pathologic finding in any age group. Twenty-four-hour ambulatory ECG recordings were recently reported on 20 young male long-distance runners during normal activities other than running. The average waking heart rate ofthis group ofhealthy individuals was 47 + 6 beats per minute, and heartratesinthe low 30s were the rule rather than the exception during the sleeping periods. Sinus pauses as long as 2.70 seconds were recorded without any symptoms (Fig 1). During the 24-hour recordings, 40% of the subjects had second-degree atrioventricular (AV) block with Wenckebach periods.8 Bradycardia in athletes has been generally attributed to increased vagal tone and decreased sympathetic activity, and even profound asymptomatic bradycardia in well-conditioned athletes can be considered a normal variant. Presumably, episodes ofAV block reflect a more marked autonomic effectonthe AV node than on the sinoatrial node in susceptible individuals. Sinus bradycardia has been a generally accepted physiologic finding in aging. Of98 elderly patients evaluatedby ambulatory monitoring, 11 had resting heart rates below 50 beats per minute. Although ectopic rhythms and tachycardias were relatively common in these apparently healthy elderly people, prolonged ventricular pauses or marked bradycardias were recorded only Fig l.-Electrocardiogram sisting for 2.70 seconds is present at a rate of

recorded from a marathon runner. are seen in the upper strip; in the lower 75 beats per minute during exercise.

Sinus strip,

pauses sinus

perrhythm

infrequently. Furthermore, even in this elderly patient populationthe most frequently demonstrated heart rates were between 50 and 100 beats per minute. ' Differentiating between extreme but physiologic sinus bradycardia and sinus node dysfunction may be difficult. Sick

Sinus

Syndrome

and

the

Tachy-bra&y

Syndrome

Bradycardia may result from a failure of the sinus node ir& pulse formation and/or conduction of the impulse through the specialized atrial, AV, or intraventricular conduction system. The basic disorders of the sinus node are sinus arrest or generator failure, and sinoatrial exit block. The sinus node receives its blood supply by a separate artery branching from the right coronary artery in 55% ofhumans and from the left circumflex in 45%. Thus, acute or chronic coronary occlusion may produce sinus node dysfunction. Pericarditis, cardiomyopathies, sarcoidosis, Friedreich's ataxia, progressive muscular dystrophy, collagen diseases, surgical injury to the sinus node, metastatic disease, and infiltrative diseases of the atria such as amyloidosis and hemochromatosis are all infrequent causes of sinus node dysfunction. A degenerative or fibrotic lesion of the sinus node and/or the specialized conduction tissue of unknown etiology is probablxthe mostfrequentcause ofthe so-called sick sinus syndrome.' Inadequate function of the sinus node or the specialized conduction tissue may be manifested by one or more of the following: (1) Persistent severe and unexpected sinus bradycardia.(2) Cessation ofsinus rhythm (sinus arrest) for short intervals duringwhich no other escape rhythm arises, or for somewhat longer periods with replacement of the sinus rhythm by an atria1 or junctional rhythm. (3) Long periods of sinus arrest without the appearance ofalower rescuing pacemaker and resultingintotal cardiac arrest. Ventricular arrhythmias may then follow. (4) Chronic atrialfibrillationbecause the sinus node is permanently silent, or repeated episodes of paroxysmal atria1 fibrillation due to cessation of sinus rhythm at these times. Atria1 fibrillation is often,but not always, accompanied by slow ventricular rate produced not by digitalis but by an accompanying organic AV block: the patient in this case has binodal disease. (5) The inability of the heart to resume sinus rhythm following cardioversion for atria1 fibrillation, most likely ifthe ventricular rate is slow, as mentioned above. (6) Episodes of sinoatrial node exit block which are not related to drug therapy. These six manifestations form the indirect evidence for the sick sinus syndrome and are its primary physiologic manifestations. There may be other abnormalities associated with this syndrome, notably a relatively high incidence of AV block and intraventricular conduction defects. It is also evident that in the bradycardic epi:4

Fig 2.-Brady-tachy syndrome. Monitored EGG strip shows perjods of sinus rest and first-degree atrioventricular heart block in the upper two tracings, ventricular premature systole in the third and fourth tracings, and supraventricular tachycardia in the fifth tracing. Alternation between bradyarrhythmias and tachyarrhythmias not uncommon: either produces symptoms.

aris

sodes in which no escape rhythm comes to the rescue, there is compromise in the function of the lower automatic centers, atria1 or junctional. These extranodal manifestations ofthe sick sinus syndrome probably reflect the extent of the basic pathologic pr0cess.l' In patients with the sick sinus syndrome the appearance of alternatingatrialbradycardia or asystolewithparoxysmalrapid heart action is quite frequent, and this symptom complex is referredto asthebradycardia-tachycardia syndrome (Fig2).These Fig with

3.-Monitored escape capture

ECG bigeminy

strip.

A 3:2 sinoatrial in the tower tracing.

block

is

seen

in

the

upper

tracing

Fig 4.--Brady-tachy syndrome associated with second-degree atrioventricular block. Leads I, II, and III are recorded in the upper row of tracings, lead I in the lower two tracings. Termination of the supraventricular tachycardia recorded by lead (middle tracing) is followed by a ventricular premature beat and two nonconducted sinus beats. Second-degree block type I is seen in the bottom tracing.

1

patients frequently present with rate-related cerebral or cardiac symptoms. An essential feature ofthe brady-tachy syndrome is dysfunction of the sinoatrial node with impaired pacemaker activity. This slow atria1 activity may represent simple sinus bradycardia with reduced pacemaker automaticity, sinoatrial exit block with long PP intervals on the ECG (being mathematical multiples ofthe faster sinus rate), or sustained sinus arrest with complete absence ofall atrialactivity (Fig 3). Since the AVjunctional pacemaker normally escapes at about 60 beats per minute,atrialbradycardia oflessthan 50 beats per minute suggests concomitant dysfunction ofthe lowerjunctional pacemaker site. The pathophysiologic factors that are responsible for the atria1 bradycardia may also contribute to the development ofparoxysma1 atrial, junctional, or ventricular tachyarrhythmias. The Fig 5:--Third-degree atrioventricular maker” is seen in the right-hand portion riods of asystole can occur even in the ‘rescuing pacemaker.”

block. of the presence

Exit block from the “rescuing pacelower tracing (aVL). Unexpected peof what appears to be an adequate

overall result is an alternating brady-tachyarrhythmia, and these wide swings in heart rate are analagous to the unstable oscillations ofan underdampened mechanical system." The basic abnormality in these patients results from a reduction in the spontaneous automaticity ofthe sinus node, or from various degrees of sinoatrial exit block. Atria1 asystole may be caused by complete loss of sinus node function, complete sinoatria1 exit block, or loss of atria1 excitability. Regardless of the type of atria1 bradycardia, the electrical abnormality may be quite diffuse and involve lower portions of the conducting system (Fig 4). When electrophysiologic techniques have been used to evaluate patients with the brady-tachy syndrome, more than 60% of them had conduction disturbances, including the intraatrial, AV nodal,orthe His-Purkinje conduction system.i'These findings indicate that the electrical dysfunction is not confined to the sinus node. Furthermore, impaired impulse formation by iower automatic centers and conduction block to the surroundlngtissue are frequent clinical findings in this setting (Fig 5). Atria1 tachyarrhythmias in the brady-tachy syndrome include such diverse entities as sinus tachycardia, paroxysmal supraventricular tachycardia, atria1 flutter, and atria1 fibrillation. The most frequent form ofsupraventricular tachycardia is probably an AV or nodal reentry circuit, in which case the tachyarrhythmia is initiated by an ectopic atria1 premature beat. There is an interesting interrelationship between the occurrence of atrialbradycardia and the occurrence oftachycardiainthe same patient. Atrialbradycardia enhances the likelihood ofthe occurrence of atria1 tachycardia. The incidence ofatrialectopic activity increases at lower heart rates. Structural and functional abnormalities ofthe nodal tissue and the atria1 conduction system, with abnormal slow conduction, areas of unidirectional block, and dispersion of the refractoriness provide the proper setting for both abnormal impulse generation and conduction and the establishment of the reentrant circuit responsible for the production ofsupraventriculartachyarrhythmias. The tachycardia, on the other hand, further depresses sinus node function by overdrive suppression, and cessation ofthe tachyarrhythmia is often followed by a prolonged sinus node recovery time with long periods of sinus arrest, during which lower pacemaker activity may be absent (see Figs 2 and 4).11 The reported incidence ofsyncope in patients with sinus node dysfunction ranges from 25% to 70%. This wide range probably reflects the fact that patients with different manifestations of sinus node dysfunction were considered. In a recentreportof828 patients with sinus node dysfunction, the incidence of syncope varied from 59% ofpatients presenting with a brady-tachy syndrome, to 45% of patients presenting with sinus arrest and/or sinoatrial block, to 33% ofpatients presenting with only persis17

tent sinus bradycardia. Two thirds of these patients had evidence of organic heart disease, including 56% with ischemic heart disease. Disturbances of impulse conduction at various levels were associated with sinus node dysfunction in one third of the patients. Syncope, present in 48% of the whole study group, was the most frequent reason for hospitalization in these patients.13 W.P. HARVEY: I have long realized the importance oflistening carefully and paying attention to what our patients tell us. This was duly impressed upon me when I started my Fellowship in cardiology. I was taking a history from an elderly lady I was evaluating in the outpatient cardiac clinic. When I asked her what was bothering her, she replied that she had been having a lot of "spells." As if to demonstrate to me, she said, "I'm having one now." At that moment, her speech stopped, her body stiffened; her eyes became a stare and rolled upward. Her hands and arms not only stiffened but trembled to some degree. This episode lasted a matter ofseconds,probably 4 or 5. She did notfallover. She promptly started talking again. A few minutes later she said, "I'm having another one." The same sequence of events just described occurred again. By this time, I was not ready to diagnose her as 3 neurotic. However, when I was listening to her heart, she had a couple of recurrent episodes, each characterized by 3 sudden cessation of the heart beat and accompanied by the signs I observed when she was relating her history; after a brief period, her heart beat returned to her former normal rhythm. The electrocardiogram showed sinus pauses which, of course, explained her clinical symptoms and signs. This was a good lesson to me, reinforcing the importance oftakingtime to listen to our patients. She was subsequently followed for 4-5 years until her death. Autopsy revealed scarring in the region of the sinoatrial node. Unfortunately the pacemaker was not available for treatment at that time. Disorders

of

the

ImpuZse

Conduction

Although sinus node dysfunction is a frequent finding in patients with syncope (as it is also in the asymptomatic population), the earliest description of transient loss of consciousness associatedwith a slowheartaction probably corresponded to AV conduction dysfunction and is now identified as the MorgagniStokes-Adams syndrome. The ECG correlate of the description by these early clinicians of syncopal episodes with or without convulsive seizures accompanied by very slow heart action, corresponds to third-degree AV block (see Fig 5). The occurrence of such a catastrophic eventin some patients prompted extensive studies ofthe AV conduction system in search ofearly ECGfindingsthat could predict which patients were at risk ofdeveloping higher degrees ofAV block. Conduction system disturbances are a common finding in symptomatic as well as asymptomatic populations. First-degree AV block with prolongation of the AV conduction time, as reflected in the lengthening ofthe PRinter-

val on the surface ECG, was found in 11 of a group of 126 healthy athletes.14 Three athletes in this population also had episodes of second-degree AV block ofthe Mobitztype I variety. This consists of the progressive prolongation of the interval between atria1 and ventricular contractions until one ventricular contraction drops out. Following a pause the AV interval is the shortest, suggesting improved conductivity. The degree of impairment of the AV conduction with each successive conducted impulse is greater, resulting in lengthening ofthe ECG PR interval, but the increment in the PR interval for each conducted impulse is less than for the preceding one, resulting in a quickeningofthe ventricular rate beforethedropped beat.This mechanism was first described by Wenckebach and is known as Wenckebach periodicity.This contrasts with a second-degree AV block of the Mobitz II variety, almost never seen in a healthy population, in which there is a sudden and transient interruption ofthe AV conduction without any disturbance ofthe preceding and following PR intervals. Mobitz originally described the high incidence of Stokes-Adams attacks as well as complete heart block in cases oftype II second-degree AV block.Mobitz II AV block is frequently associated with wide QRS complexes on the ECG, indicatingthatthelevelofconductionblockis actually below the AV node in the His-Purkinje system. Although the surface ECG is frequently inaccurate to describe the level of AV block, the unfavorable prognostic significance of type II seconddegree AV block with wide QRS complexes has long been recognized, with a high incidence of episodes ofthird-degree block in these patients (see Fig 5).15 The infranodal intraventricular conduction system consists of three functioning fascicles: the right bundle-branch, and the anterior and posterior fascicles of the left bundle-branch.'" Bifascicular block may thus be defined as right bundle-branch block with left anterior hemiblock, right bundle-branchblock with left posterior hemiblock, or left bundle-branch block. When in addition to these findings there is a prolonged AV conduction time, or alternating left and right bundle-branch block, this is called trifasicular block, and these patients have been considered to be especially at high risk of developing complete heart block. Though the occurrence ofsyncope in patientswithbifascicular ortrifascicular block suggests progression ofthe conduction disease to third-degree complete AV block-and this progression has been documented in some cases-the natural history of "high-risk" bundle-branch block was not clearly defined until recently. When 554 patients with chronic bifascicular and trifascicular conduction block were followed for more than 3 years, heart block occurred in 19 patients, and the actuarial 5-year mortality from an event that could conceivably have been a bradyarrhythmia was 6%. Ofthe 160 deaths, 42% were sudden, 19

but most of these were not due to bradyarrhythmia and heart block but to tachyarrhythmia and myocardial infarction. Patients with "high-risk" bundle-branch block and syncope had a 17% incidence ofheart block, as opposed to 2% in those without syncope. However, no single variable was predictive of which patients were at high risk of death from a bradyarrhythmia. Mortality was higher in patients with coronary artery disease and congestive heart failure. Thus, it appears that the major determinants for total mortality and sudden death is the underlying cardiac disease, particularly coronary artery disease, and the status ofthe cardiac function,ratherthanthe bundle-branch block per se. Patients with prolonged PRintervalinthese studies were also shown to have a higher risk of sudden death. Except for a prolonged PRinterval, a death conceivably due to bradyarrhythmia could not be predicted from any clinical, EGG, or even electrophysiologic finding or any combination of such findings.'? This conclusion has important implications for the diagnostic evaluation ofthese patients and also for the indications ofpacemaker therapy. These will be discussed in a later section ofthis review. For now it should be emphasized that the presence of bifascicular ortrifascicular bundle-branch block on the ECG of a patient with a history ofsyncope is not necessarily an ominous finding. In a recent study of186patients with such a block,the clinical course ofthe 30 patients with syncope was surprisingly benign. Only 20% of these individuals had bradyarrhythmia that could havebeenpreventedbypermanentpacing,andinthe remaining 24 patients,either no cause ofsyncope could be shown or causes not amenable to permanent pacing were found. The risk ofsudden deathinthe syncope patients was relatively small,lessthan 5% in a year of follow-up, except for the patients with left bundle-branch block, in whom the risk ofsudden death was approximately 19%. Furthermore, the risk of sudden death in the patients with syncope was equivalent to that in the patients with similar findings ofbifascicular bundle branch-block and without syncope. In patients with syncope possibly caused by ventricular arrhythmias and patients in whom the cause ofsyncope was unknown, recurrent syncope was not noted during follow-up.18 Exit block from subsidiary rescuing fascicular pacemakers can produce long periods ofasystoleinthe presence ofunderlying highgrade AV block (see Fig 5). Tachyarrhythmias

Both ventricular and supraventricular arrhythmias may be associated with CNS symptoms. The mechanism by which tachyarrhythmias produce decreased cardiac output is always similar. When a critical heart rate is reached the diastolic filling 20

period of the left ventricle decreases and the increased heart rate no longer compensates for the decrease in diastolic filling. Consequently, the cardiac output decreases, and the development of symptoms of decreased perfusion is dependent on the amount ofpreexisting cerebrovascular disease and the extent to which the cardiac output is decreased-The degree ofimpairment of cardiac output is even greater in ventricular arrhythmias, where the normal sequence of activation of the atria and the ventricles is lost. In the case of independent atria1 and ventricular activity, not only will the diastolic filling volume be decreased because of the loss of atria1 contribution, but when the atria1 and ventricular contraction occur simultaneously or very close in time, part of the ventricular stroke volume will be regurgitated toward the atria as well as the pulmonary and systemic venous systems, with an even greater drop in the cardiac output and the development ofsystemic and pulmonary congestion. Therefore, it is very difficult to predict a critical heart rate at which cerebral symptoms will develop in an individual patient, as this depends on the possible preexistence ofcerebrovascular disease, the underlying cardiac process that precipitated the tachycardia, the contractile status of the left ventricle, whetherthetachycardia is ventricular or supraventricular, and the sequence ofventricular and atria1 contraction. Long-term ECG monitoring ofinpatients and ambulatory Holter monitoring of outpatients are the most widely used methods of detection of spontaneously occurring arrhythmias in patients with a history of syncope. The finding of any specific arrhythmias by long-term monitoring carries a double significance: it may explain the patient's symptomatology and, therefore, direct a therapeutic efforttowardthe suppression ofa specific tachyarrhythmia; and in the case of potentially life-threatening arrhythmias it may offer some prognostic value to evaluate the risk of sudden death. However, caution in the interpretation of long-term ambulatory or inpatient ECG monitoring is required. It is well known that unselected, presumably healthy populations have a high incidence ofsupraventricular and ventricular ectopic rhythms. The frequency of arrhythmias on 6-hour ECG recordings of 301 actively employed asymptomatic men with a median age of 55 years was 76% for supraventricular arrhythdepolarizations and supraventricular mias (atria1 premature tachycardia) and 62% for ventricular arrhythmias (ventricular premature depolarizations, ventriculartachycardia, and ventricular bigeminy)." Because significant arrhythmias are detected so frequently in both asymptomatic and symptomatic patients,one must be careful to avoid attributing a symptom to an arrhythmia unless a close temporal relationship can be demonstrated. In a recent study of518 consecutive 24-hour ECG recordingsin patients 21

with a variety of cardiovascular complaints, the correlation of cardiac arrhythmias on the 24-hour recordings with the cardiovascular complaints was 13%. Furthermore, in 34% of these patients the typical symptoms were associated with a normal ECG. including supraventricuIn the same study major arrhythmias, lar and ventricular tachycardias, often occurred in the absence of symptoms: 44 of 54 episodes of supraventricular tachycardia recorded were asymptomatic and 37 of 40 episodes of ventricular tachycardia were also asymptomatic. Actually, only 3 of 40 patients who had recorded ventricular tachycardia became symptomatic concurrently with this arrhythmia.2” This study emphasizes the importance of establishing a temporal relationship between the syncope and the arrhythmia when there is a suspicion that the arrhythmias may be causing the cerebral symptoms. M.A.

ENGLE:

incidence the authors’ a temporal adults. It prolapsing emphasis

times patient

of

silent caution relation is especially mitral on the

This

is particularly significant information, the high arrhythmias in healthy men and women, .as well as in attributing the symptom to the rhythm unless is established. This is true in children as well as in important in relation to the frequently diagnosed valve syndrome and what I believe is often an overassociation with significant arrhythmias and some-

overtreatment for the rhsthm

of the patient of his heart.

or undue

creation

of

concern

by

the

The prognostic significance of arrhythmias recorded on longterm ECG monitoring must be interpreted with extreme caution. In patients with heart disease the presence of premature ventricular beats on a standard ECG is associated with a small but statistically significant increase in mortality, but in the absence of clinical heart disease, premature ventricular contractions seem to have little effect on mortality.21 In 37 patients with nonsustained ventricular tachycardia discovered on ambulatory monitoring, only 19 with the diagnosis of congestive cardiomyopathy or a history of congestive heart failure were found to be at increased risk of sudden death. In fact, while 9 of these 19 patients died suddenly during an average follow-up of 19 months, only 1 of the remaining 18 patients with a variety of diagnoses died suddenly in the follow-up period. No ECG characteristic of the ventricular tachycardia, including beats per episode, episodes per day, rate, prematurity of the initiating ectopic beat, or the occurrence of associated arrhythmias, was an important prognostic marker.22 Impaired Any transient example ^^

Nemodynamics and number of hemodynamic drop in cardiac output is aortic stenosis, in

Obstruction to F’zow derangements may cause resulting in syncope. The classic which, by virtue of the decreased

a

and relatively fixed cardiac output produced by the organic obstruction to the outflow of the left ventricle, an increase in the metabolic requirements such as during exercise may result in a sudden decrease of the cerebral perfusion and syncope. The mechanisms precipitating effort syncope in aortic stenosis are probably manifold, shared by other forms of obstruction to the left ventricular outflow and also at least partially by severe coronary artery disease in which global ischemia may occur during exertion. Systemic vascular resistance normally declines during exercise as a consequence of arteriolar dilation. Under normal circumstances this drop in peripheral vascular resistance is compensated forbythe normalincreasein cardiac outputandtherefore of arterial pressure during heavy exertionHowever, in the severe forms ofheart disease in which cardiac output rises proportionately less than vascular resistance falls, arterial pressure declines, with consequent cerebral ischemia and syncope. In patients with aortic stenosis, this sequence is probably aggravated by an exaggerated peripheral vasodilatory reflex resulting from the high pressure on left ventricular baroreceptors, with blunting of the corn ensatory carotid and aortic baroreceptor-meB diated reflexes2 W.P. HARVEY: Concerning valvular obstruction, it is logical that the closer the stenotic valve to the brain, the more likelihood ofoccurrence ofdizziness and/or syncope; hence, aortic valve or outflow obstruction is the culprit. Similar mechanisms may operate in aortic subvalvular stenosis and also in idiopathic hypertrophic cardiomyopathy (ASH). In ASH the obstruction to the outflow tract ofthe left ventricle is dynamic, and it is exacerbated by increased contractility and decreasedleftventricularvolume.Therefore,drugs withpositive inotropic effects, such as digitalis or arterial and venous vasodilators, or a decrease in ventricular filling,such as produced by the Valsalva maneuver may precipitate episodes ofhypotension and syncope (Fig 61. In patients with marked left ventricular hypertrophy, a decreased left ventricular compliance with impairmentofthe diastolic filling may result in a further decrease in cardiac output. Syncope in patients with left ventricular outflow obstruction is not always associated with exertion; contributing arrhythmiasin additiontothe altered hemodynamics may play a decisive role in the precipitation ofsyncope (Fig 7).z4 Rare causes ofsyncope produced by obstructiontothe ventricular inflow or outflow are atria1 myxomas and other tumors Clinically, the atrialtumors most commonly simulate the hemodynamic events encountered in mitral stenosis or mitral insufficiency. Atria1 myxomas can cause obstruction to pulmonary or systemic venous flow, and they can intermittently impair chamber emptying and proper functioning of the mitral or tricuspid 23

200

100

0

Fig 6.-Hypertrophic cardiomyopathy. Tracing at left shows lead It aortic pressure (AO) and left ventricular pressure during sinus rhythm and in the resting recumbent state. Tracing at right shows gradient of more than 100 mm Hg between the aorta and left ventricular cavity during a Valsalva maneuver in a patient with asymmetric septal hypertrophy. Obstruction to the outflow tract of the left ventricle is present in this instance. Fig 7.-Electrocardiogram from same patient as in Figure 6, following a premature ventricular systole (seen on lead II, top of tracing): the aortic valve fails to open. Following the long pause with enhanced filling of the left ventricle and peripheral vasodilation, as seen in the aortic pressure curve, a gradient occurred between the aorta and the left ventricular cavity that persisted for several beats.

valve. A helpful differential clinical feature is the intermittent clinical pattern of mitral or tricuspid obstruction. Episodes of syncope, shortness of breath, or cardiac murmurs associated with a change in body position are typical of this disorder. An echocardiographic study of50 patients with intracardiac myxomas revealed that 86% ofthese were confined tothelefi atrium and 10% to the right atrium; there was one case of right ventricular myxoma and one case of multiple myxomas in the left atrium and the left ventricle. 25 Although intracardiac myxomas are an extremely rare cause ofsyncope and the incidence ofintracavitary myxomas is unknown, the diagnosis ofthis disorder is easily made by echocardiography and the hemodynamic impairment

corrected

by

surgery.

W.P. HARVEY: lntracavitytumor, especially myxoma may cause syncope or dizziness. Ifthere are signs oftricuspid stenosis and the patient has syncope, be sure to rule out myxoma ofthe right atrium which at times obstructs the orifice ofthetricuspid valve. Tricuspid valvular stenosis The myxoma,

due

same

to rheumatic applies to mitral as this is more

etiology valve likely

is much stenosis the cause

less and rather

matism. ORTHOSTATIC Failure regulation

HYPOTENSION of the normal is a common

AND mechanisms and often

RELATED of

likely to cause syncope-always than being due

syncope. rule out to rheu-

MECHANISMS supine

blood

pressure

overlooked cause of syncope. The normal hemodynamic changes on assumption of the erect position consist of a transient decrease in systolic arterial pressure of up to 25 mm Hg with no major changes in the diastolic pressure and a possible increase in the heart rate by 5 to 25 beats per minute. These changes are brought about by stimulation of sympathetic and inhibition of parasympathetic reflexes, as manifested by (1) reflex arteriolar constriction mediated through baroreceptors in the carotid sinus and aortic arch, (2) venoconstriction and augmentation of respiration to facilitate Venus return to the heart, (3) reflex acceleration of the heart rate, (4) an increase in muscle tone and tissue pressure in the legs and abdominal muscles, and (5) an immediate increase in catecholamine levels and delayed activation of the renin-angiotensin-aldosterone system.26 Postural maladjustment is sometimes found in young people oftall asthenic habitus who are otherwise healthy. It is also frequent among the elderly whose postural reflex responses are slowed by physiologic aging. Prolonged bed rest with disuse of the postural reflexes, pregnancy, physical exhaustion, and hot weather, with reduction in circulating vascular volume, are all conditions that favor the development of poor postural adjust25

ment. All these conditions result in an abnormal decreaseinthe systolic pressure and an excessive accelerationinthe pulse rate when the upright position is assumed. Fright, pain, or other powerful emotions may produce weakness, nausea, sweating, pallor, and occasionally syncope in susceptible individuals, accompanied by bradycardia (cardioinhibitory reflex) and/or hypotension (vasodepressor reflex), usually in the upright position. Orthostatic hypotension may be secondary to autonomic dysfunction with lack ofa concomitant increase in heart rate due to inactivation of the normal cardioaccelerator reflex associated with the assumption of the upright position. In contrast, in orthostatic hypotension due to volume depletion, with intact autonomic function, standing induces prolonged tachycardia through a compensatory increase in sympathetic activity. On assuming the upright position, patients with orthostatic hypotension complain of lightheadedness, faintness, blurring, or even loss of vision, a sense of profound weakness, and unsteadiness. Approximately half of the patients will lose consciousness at maximal blood pressure drop. Usually the syncopalepisode lasts no longer than seconds but on rare occasions it has lasted several minutes. The syndrome oforthostatic hypotension may be secondary to adrenalcorticalinsufficiency, pheochromocytoma, or primary aldosteronism or may be a manifestation of autonomic neuropathy, as in diabetes, primary amyloidosis, or porphyria. In these latter instances orthostatic hypotension is frequently accompaniedbyimpotence as well as dysfunction ofthebladder andbowels.Primary disorders ofthe central and peripheral nervous systems that may cause orthostatic hypotension include intracranial tumors, multiple cerebral infarcts, Wernicke's encephalopathy, tabes dorsalis, syringomyelia, the chronic and acute polyradiculoneuropathies, inflammatory myelopathies, and polyneuropathies secondary to carcinoma, uremia, and alcoholism. Orthostatic hypotension without autonomic dysfunction may result from acute blood loss, anemia, hypovolemia, electrolyte imbalance (especially sodium and potassium depletion), and the use of various psychotropic and antihypertensive drugs. Among these are the phenothiazines, tricyclic antidepressants, peripheral adrenergic blocking agents such as guanethidine and prazosin, methyldopa and other centrally acting antihypertensive drugs, and diuretics, all ofwhich may cause syncope, especially in patients with restricted dietary sodium intake.26 A rare disorder that may cause syncope is primary or idiopathic orthostatic hypotension, which when accompanied by neurologic manifestations is referred to as the Shy-Drager syndrome. Idiopathic orthostatic hypotension afflicts men three or four times as often as women and is a chronic and slowly developing disease. Lightheadedness or faintness is often accompa26

Fig S.-Effect rate. Note the ing the Valsalva of the tracing.

of Valsalva maneuver on the brachial artery pressure decrease in the brachial artery pressure from 100 to 60 mm with a typical overshoot seen in the right-hand maneuver,

and heart Hg followportion

nied by urinary retention or incontinence and impairment ofpotency and libido, penile erection, and/or ejaculation. Symptoms such as nausea, pallor, and cold perspiration, which require an intact autonomic nervous system, are conspicuously absenL2" The integrity ofthe sympathetic nervous system can be evalIn healthy subjects this mauated by the Valsalva manuever. neuver results first in a slight increase in blood pressure due to transmission of the increased abdominal pressure to the aorta, followed by a decrease in mean arterial and pulse pressures, attributed to a decrease in venous return and cardiac output, which levels off quickly. After cessation ofthe forced expiration, there is a further drop in blood pressure when compression is suddenly removed from the aorta. This is followed by resumption of normal cardiac output into a constricted arterial bed, giving rise to the so-called hypertensive overshoot, followed by reflex bradycardia as a response to the sudden elevation in blood pressure (Fig 8). In cases of orthostatic hypotension due to sympathetic failure, the forced expiration involved in the Valsalva maneuver causes an exaggerated fall in blood pressure, with only slow increase of the arterial pressure at the end of forced expiration and without the characteristic overshoot. Also, reflex bradycardia does not occur. Another, easier way ofstudying efferentsympathetic functionisby means ofthe cold pressor test, which is performed by immersing both feet for 1 minute in water maintained at 10 C. The normal response, an increase in blood pressure mediated by reflex vasoconstriction, is absey$ in patients with failure of the normal sympathetic response. 27

SHORTAGE METABOLIC

OF ENERGY MECHANISMS

SUBSTRATES

AND

RELATED

Loss ofconsciousness frequently results from inadequately low concentrations oftwo critical constituents in the blood perfusing the brain, oxygen and glucose. Actually, if syncope is strictly defined as a transient loss of consciousness, these mechanisms are unusual causes of syncope. The loss of consciousness caused by hypoxia or hypoglycemia usually persists for a longer period of time, but hypoxemia and hypoglycemia can be contributing factors in patients with compromised cerebral circulation for other various reasons. A somewhat related but different mechanism for syncope occurs in the hyperventilation syndrome. In this case, hypoxia of the brain is indirectly produced by cerebral vasoconstriction as a result of respiratory alkalosis. Hyperventilation produces a fall in the arterial PCO, which inturnincreasesthe pH ofthe blood. Alkalosis produces peripheral vasodilation by a direct effect on the peripheral resistance vessels. This fall in peripheral vascular resistance is normally compensated by a rise in the heart rate andcardiac output,maintainingthe blood pressure at arelatively stablelevel.The effectofalkalosis onthe cerebralvesselsis opposite to the effect on the peripheral vessels. Cerebral vasoconstriction, with a stable arterial pressure, produces a decreased net perfusion pressure ofthe brain and results in syncope. Although most frequently observedin overtly anxiousindividuals, overbreathing or hyperventilation may significantly contribute to the symptoms of the psychologically stable patient, especially one suffering from organic illness. Patients with pain, especially those with angina, may find temporary reliefoftheir symptoms by deep and frequent breathing. After a variable length of time, the patient with hyperventilation notes numbness and tingling of his hands and around his lips with occasional twitching and tightening of the muscles of the face and forearms. Ifthe overbreathing continues, the patient may experience presyncopal symptoms and eventually lose consciousness. He or she will promptly recover when the metabolic abnormalities are reversed by the hypoventilation that occurs during the syncopal period. M.A. ENGLE: Rebreathing Eo‘urthose hyperventilating fainted. CAROTID

SINUS

in a paper bag is a traditional individuals who are faint but

maneuver have not yet

HYPERSENSITIVITY

The carotid sinus regulation of heart 28

plays an important rate and peripheral

role in the normal vascular resistance.

reflex An

increase in intraluminal carotid pressure produces a slowing of the heart rate and a decrease in systemic arterial blood pressure. Accordingly, carotid sinus stimulation in a normal subject produces two different types of responses. The first is cardioinhibitory in nature:vagalstimulation causes slowingofthe heart rate by a direct effect on the sinus node, and various degrees of AV block by an effect on the AV node. This in turn may result in a decreased cardiac output, with a resultant decrease in the cerebral blood flow. The second effect of carotid sinus stimulation is an inhibition of the sympathetically mediated vasoconstriction. This is the so-called vasodepressor effect, which produces peripheral vasodilation with a marked fall in the peripheral resistance and the effective perfusion pressure ofthe brain. Atropine in this case will prevent the bradycardia but will not affect the fall in the blood pressure.c7 Carotid sinus hypersensitivity, as well as other mechanisms that can cause syncope in susceptible individuals, is a frequent finding in the general population. Even though this syndrome is to be suspected in patients with a history of lightheadedness and syncope on sudden turning or hyperextension of the neck, here, too, a strict temporal relationship must be established between carotid sinus stimulation on one hand and the cardiovascular effects and syncope on the other before concluding that this mechanism is responsible for syncope in a particular patientDriving an automobile in reverse, shaving the neck, and wearing tight collars have also been associated with the syncopal symptoms in patients with carotid sinus hypersensitivity. W.P. HARVEY: In my experience, a hypersensitive carotid sinus is an uncommon cause of d&&ess and syncope, although it certainly does occur. I recall an interesting patient, a chef at one ofthe local hospitals who had recurrent syncopalepisodes. At the time ofour evaluation,he already had previous laboratory studies including electrocardiograms, monitoring had been

ofhis cardiac documented.

rhythm

and

cerebralarteriography.

No

cause

He stated that his last episode of syncope occurred when he was shaving. Remembering this, when listening to his heart, his carotid sinus was gently massaged-immediately the heart beat stopped and returned after a few seconds. The electrocardiogram was attached, and as the tracing was being taken, a tongue blade was moved with some pressure applied over the region ofhis carotid sinus (thereby abruptly

documented, importance

simulating stopped

the beating

of course, ofa

careful

Also "handed down" the streetcar conductor turned his trolley, not in the opposite luloid or starched

use for

of his razor a briefperiod

on the

while and

electrocardiogram.

detailed

he then

shaved).

The

heart

resumed. This This illustrates

history.

in medical anecdotes folklore is the example who would get dizzy (or faint) only when

looking in one direction. This neck collar that

was the of he

direction (probably to the right), but was due to the conductor's high celpressed on the carotid sinus thereby 29

producing

dizziness or syncope. I was told about of a streetcar in Boston. I suspect the a conductor in some ofour other cities.

conductor about

this

as

same

relating

story

was

to a told

Since some slowing of the heart rate and a decrease in the arterial blood pressure are almost universal findings with carotid sinus stimulation in the general population, fairly strict criteria must be met before a patient's symptoms can be directly attributed to carotid sinus hypersensitivity. Cardioinhibitory carotid sinus hypersensitivity was defined as ventricular asystole for more than 3 seconds during carotid sinus stimulation. The vasodepressortype of carotid sinus hypersensitivity was considered to exist when there was a decrease in systolic blood pressure of50 mm Hg or greater with no associated cardiac slowing, or when the decrease in systolic blood pressure was greater than 30 mm Hg and the patient's symptoms were reproduced (Fig Y).= Even with these strict criteria for the diagnosis of carotid sinus hypersensitivity, it is often difficultorimpossibleto distinguish primary abnormalities ofthe carotid sinus from an abnormal response of the sinoatrial node or the conducting tissue to its stimulation. Patients with sinus node disease or with various degrees ofAV block show an abnormalresponseto carotid sinus stimulation

even

in

the

absence

of

a primary

carotid

sinus

ab-

normality. Notably, several different mechanisms may be operational to produce symptoms in a particular patient. The combination ofboth types of abnormal response to the carotid sinus stimulation may be missed unless carotid sinus stimulation is repeated after the administration of atropine or temporary pacing. Fig S.-Carotid sinus hypersensitivity. sinus pressure (CSP) in the presence systolic pressure from 94 to 68 mm sequential pacing, which returned the

Electrocardiogram shows effect on carotid of vasodepressor syncope. Note fall in the Hg prior to the institution of atrioventricular systolic blood pressure to 80 mm Hg. #AV

-A-

I I I i I

.JA

SEQUENTIAL

PACtNCI

The incidence of sinus node disease in patients experiencing syncope during carotid sinus stimulation is unknown, but when 67 patients were studied with programmed electrical stimulation techniques, 16% developed paroxsymal atria1 fibrillation during atria1 stimulation, and 39% had a prolonged sinus node recovery time after overdrive suppressionby rapid atria1 pacing, suggesting sinus node dysfunction. Likewise, 20% of the patientshad a prolonged infranodalconduction time manifestedby an HVintervalofmorethan 60 mseczs Identification ofthe primary defect may be important in some patients with carotid but in others it is somewhat academic. The pasinus syncope, tient that has a significantdropin blood pressure andheartrate on carotid sinus stimulation and a marked improvementor disappearance of the symptoms when the heart rate is restored to normal with atropine or pacing with a lesser dropinthe arterial blood whether

pressure the

conduction

is primary

system,

clearly defect

a candidate is localized

or in the

carotid

for in

sinus

the

permanent sinus

(see

Fig

node,

pacing, in the

9).

W.P. HARVEY: Personally observed which I don't recall reading or hearing discussed, is that a-patient with si-ificant aortic stenosis may develop a hypersensitive carotid sinus following digitalization; in fact it, may be strikingly so. If there is true hypersensitivity, very gentle carotid sinus pressure is,as a rule, all that is required to produce slowing ofthe heart beat. Also of great importance are these words of caution concerning carotid sinus stimulation: It is always wise to place one's stethoscope on the precardium so as to be listeningtothe heart whenever pressure on the carotid sinus is applied with one's finger, or fingers. In this way, any change in heart rhythm is immediately appreciated and carotid pressure should cease. Clinically, the right carotid sinus is usually more sensitive than the left. CLINICAL CORONARY

Although nary artery

SETTINGS

IN

ARTERY

DISEASE:

the true disease

WHICH

incidence is unknown,

SYNCOPE ACUTE

OCCURS

AND

ofsyncope there

CHRONIC

in

patients with coroa number ofphysiopathologic mechanisms by which coronary artery disease may produce syncope. During the acute coronary event, sudden failure of the pump function of the left ventricle may produce a decrease in the perfusion pressure of the brain, leading to loss ofconsciousness. Ifthese changes in the left ventricular function are compensated for by opposite changes in the peripheral vascular resistance, the loss ofconsciousness may be transient and result in a syncopal episode. A more common mechanism for syncope during an acute myocardial infarction is rhythm dist.urare

31

Carotid

Fig lO.-Arrhythmias effect of vagal stimulation ular conduction in the long periods of asystole sage.

Sinus

Massage

in

acute myocardial infarction. Electrocardiogram shows the in the presence of atrial tachycardia with 2:t atrioventricpresence of an anteroseptal waif myocardial infarction. Note due to second-degree AV block following carotid sinus mas-

bances, especially ventricular tachycardia and fibrillation. The incidence of death from sudden arrhythmias in patients with acute myocardial infarction has decreased significantly since careful monitoring in coronary care units, prophylactic treatment of ventricular tachyarrhythmias, and aggressive management of the myocardial electrical instability associated with acute myocardial infarction have become common clinical practice in this country. Bradyarrhythmias are also common in patients with acute myocardial infarction These arrhythmias might be secondary to vagal influences in the so-called bradycardia-hypotension syndrome.Inthe presence ofinferior or posterior myocardialinfarction, occlusion of the terminal coronary branches supplying the sinus or AV nodes may result in extreme sinus bradycardia and/ or AV block. (Figure 10 demonstrates AV block produced by carotid sinus pressure in the presence ofa supraventriculartachycardia.) Blood is supplied to these structures by a single artery in each case, a branch ofthe right coronary artery in more than 50% of cases and the left circumflex in the remaining. Some of these patients might require temporary or permanent pacing, but the bradycardia-hypotension syndrome is due to vagalinfluences in the majority of patients, and in this case they respond favorablytothe administration ofatropine and expansion ofthe intravascular volume. Sixty-eight (17%) of 308 patients admitted to a hospital with acute myocardial infarction had the bradycardia-hypotension syndrome, defined as a ventricular rate below 60 beats per minute and a systolic blood pressure of less than 100 mm IIg. Sixty-one of these 68 patients responded to the administration of atropine with a significant increase in

heart rate and systolic blood pressure, which is interpreted as anindicationthatthese manifestationswerein fact due to vagal influences. Sixty-nine percent of these patients had symptoms referredtothe CNS, 11% havin 3ffrank syncope and 58% having dizziness and lightheadedness. Tachyarrhythmias and bradyarrhythmias that occur in the setting of an acute myocardial infarction require aggressive management, especially when these arrhythmias are responsible for signs of cerebral hypoperfusion. However, management of tachyarrhythmias and bradyarrhythmias in the population with chronic coronary artery disease is more controversial. All of the arrhythmias discussed earlier in this monograph occur more frequently in patients with coronary artery disease. For example,when a population of539 patientswith premature ventricular contractions on routine EGGS were studied, about half demonstrated some evidence of cardiovascular disease, and about half of these had ECG evidence of a previous myocardial infarction or a history ofangina pectoris. Althoughtheincidence of premature ventricular contractions in a control population without coronary artery disease was also high and similar to that in patients with presumed coronary artery disease, the mortality at the end of 3K years was higher for patients with evidence of coronary artery disease. In fact, in the absence of clinical heart disease and other ECG abnormalities, ventricular premature contractions appear to have little effect on mortality. On the other hand, the mortality of patients with myocardial infarction was 40% in the group with ventricular premature beats versus 23.1% in the patients without, and 37.5% versus 26.3% in patients with angina pectoris in the groups with and without premature ventricular contractions, respectively.21 Although these results seem to indicate that the presence ofventricular tachyarrhythmias in patients with coronary artery disease indicates a poor prognosis, when strict invasive criteria for the diagnosis of coronary artery disease are employed and the presence and complexity of ventricular arrhythmias on 24-hour ambulatory monitoring as well as invasive parameters of left ventricular function are correlated with the prognosis, it can be appreciated that a strong correlation exists among the presence of complex arrhythmias, poor left ventricular function, and an unfavorable prognosis. In a study of395 patients with signficant coronary artery disease and ventricular arrhythmias detected during 24-hour ambulatory monitoring, the ventricular arrhythmias per se did not contribute any prognostic information. Furthermore, the ejection fraction at the time of cardiac catheterization was more useful than the arrhythmias for identifying patients athigh risk ofsudden death.31 Even when patients with ventriculartachycardia are considered, only the patients with a history ofcongestive cardiomyopathy or congestive heart failure 33

Fig sinus with beats

Il.-The effect of early premature systoles node. In this instance the ventricular premature a peripheral pulse. Consequently, the effective per minute, which was associated with syncope.

rn

the presence systoles were pulse rate in this

ot depressed not associated patient was

22

are at high risk for sudden death.” However, the combination of ventricular ectopic beats and a sinus bradycardia or sick sinus syndrome could affect the minute volume and produce syncope, especially if stroke output of the ventricular premature beat is inadequate (Fig 11). The issue of ventricular ectopy in an outpatient population is complex and extremely important in the evaluation and management of patients with syncope, especially in light of the high incidence of premature ventricular contractions in the asymptomatic middle-aged population. This incidence has been found to be 62.2% during a continuous ECG 6-hour recording.‘” Although ventricular tachyarrhythmias were found to be an important factor in the production of syncope (they were etiologically related to its occurrence in 13 of 39 cases of syncope of cardiac origin), ischemic heart disease per se does not carry the same prognostic significance, since 20 of the 51 patients that were classified as having unexplained syncope also h&d a diagnosis of ischemic heart disease.4 The incidence of coronary artery disease is equally high in patients with other conditions potentially capable of producing syncope . This was found to be 51% in patients with the bradytachy syndrome,l’ and coronary artery disease has been etiologically related to the production of high-risk bundle-branch block m 39% of the patients-l7

MITRAL

VALVE

PROLAPSE

Mitral valve prolapse refers to a vaguely defined association of various signs and symptoms, with a specific ECG pattern of abnormal movement of the mitral valve during systole. The true incidence of mitral valve prolapse in the general population is unknown and the incidence found by different authors depends heavily on the diagnostic criteria employed, varying between 1% and 10% of the population. Common symptoms in patients with mitral valve prolapse include atypical chest pain or chest discomfort, palpitations, fatigue, lightheadedness, and, rarely, syncope. Frequently, a midor late systolic click, a series of systolic clicks, or a click in association with a late systolic murmur are 34

recognized on a routine physical examination, andthe diagnosis is then confirmedby an echocardiogram. A majority ofthese patients are asymptomatic, and there is no certainty about whether these cases represent a discrete clinical syndrome or a normal variant. Occasionally patients with mitral valve prolapse have serious and even life-threatening complications consisting ofvalvular endocarditis, valvular insufficiency, ruptured chordae tendineae, and an unknown incidence oflife-threatening arrhythmias and sudden death. When syncope occurs in a patient with mitral valve prolapse, there is a tendency to attribute the sudden loss of consciousness to supraventricular or ventriculartachyarrhythmias known to be associatedwiththis syndrome. When 24 patients with echocardiographic evidence of mitral valve prolapse were studied with 24-hour continuous ECG monitoring and exercise test, approximately halfofthe patients showed more than one premature ventricular contraction on the treadmill test and frequent premature ventricular contractions on the ambulatory ECG.The majority ofthese patients had complex ventricular arrhythmias, including ventricular tachycardia. Interestingly, there was a general lack of patient awareness ofthe recorded arrhythmias and also a frequent lack ofrecorded arrhythmias durin @he subjective experience ofpalpitations in this patient group. In a recent study of20 patients with mitral valve prolapse, frequent and complex ventricular premature contractions were present in 40% of the patients, sinus tachycardia or premature atria1 contractions in 20%, and episodes of abrupt unexplained sinus bradycardia, periods of sinus arrest, or exaggerated sinus arrhythmia in 30%.33 Systemic and cerebral emboli have also been observed in patients with mitral valve prolapse (probably related to the presence of arrhythmias), and this may explain some cases ofsyncope. W.P. HARVEY: Consideringthelarge number ofpeople who have mitral valve prolapse (some estimates as high as 15,000,OOO in the United States), syncope is rare,asisthe case with the overemphasized, sudden death. Currently, I am following a patient with mitral valve prolapse who about 5 years ago had a near syncopal episode while she was driving her car in heavy traffic. Several ofher children were with her and fortunately, she was able to steer the car offthe highway and safely stop. She has been matic; however of a recurrence.

treated it took

with about

Congestive cardiomyopathy tained ventriculartachycardia

propranolol 3 years

has as

for

since her

and has been to drive without

been associated well as sudden

with

asymptothe fear

nonsus-

death."'There35

fore, syncope in patients with congestive cardiomyopathy could be considered an ominous symptom and animportantrisk factor for sudden death. Also, in congestive cardiomyopathy as in any severe form of heart disease, syncope precipitated by exercise may be due to an inadequate increase ofthe cardiac output, associated with a fall of peripheral vascular resistance and a consequent decline in arterial pressure, resulting in cerebral ischemia. Let us consider the special case of the patients with ASH. In these patients syncope might be precipitated by severalmechanical and electrical factors. In patients with hypertrophic cardiomyopathy, as in patients with aortic stenosis, outflow obstruction of the left ventricle associated with an inadequate rise in cardiac output during exercise might be responsible for syncope. This hemodynamic derangement is further aggravated by the impaired diastolic filling associated with decreased left ventricular compliance. However, syncope in patients with hypertrophic cardiomyopathy is probably more frequently precipitated by arrhythmias (see Fig 7). Eighty-eight percent of33 patients with ASH studied by long-term Holter monitoring were found to have arrhythmias, which were potentially life-threatening in 39% of cases. A history ofsyncope was recorded in 12 patients, presyncopein 27, and palpitationsin another 23 individuals. All these patients had symptomatic obstructive hypertrophic cardiomyopathy and received large doses ofpropranololatthe onset of the study. Pacemaker insertion or additional antiarrhythmic therapy was requizedin 10 ofthese patients for arrhythmia control during a mean follow-up of 4.7 years. These patients received significant benefit from suppression of their potentially life-threatening arrhythmias, with a significant decrease in palpitations and episodes ofpresyncope and complete elimination of syncope and sudden death during follow-up. Thus, Holter monitoring and stress testing should be employed in all patients with hypertrophic cardiomyopathy to detect and manage potentially life-threatening arrhythmias. OTHER

FORMS

OF HEART

DISEASE

Many forms of heart disease, if severe enough, may result in syncope. Earlier we discussed the significance of syncope in patients with aortic stenosis, coronary artery disease, and different forms ofcardiomyopathies. In subjects with congenital heart diseases such as tetralogy of Fallot, patent ductus arteriosus, and interventricular orinteratrialseptal defects,syncopeis common. It is particularly apt to occur following effort or cryingininfants and young children, with sudden reversalofaleft-to-right shunt and, consequently, a fall in the arterial oxygen saturation. Val-

vular diseases other than aortic stenosis may also infrequently result in syncope. This is particularly true for mitral or pulmanic stenosis. Dissecting aneurysms of the aorta may produce syncopal attacks when they involve the arch of the aorta with encroachment upon the innominate or carotid arteries, thus leading to diminished blood flow and cerebral anoxia. Occasionally a combination ofevents, e.g., sinus bradycardia with persistent ventricular premature systoles devoid ofstroke output,may reduce the minute volume and produce syncope (see Fig 11). A.C. DE LEON: Primary entity which may present As a rule, uncomplicated, PDAf do not present with iology results in syncope monary vascular changes.

pulmonary hypertension is another clinical with syncope. left to right central shunts (ASD, VSD, and syncope. Development of Eisenmenger physas a clinical manifestation ofthe severe pulp

W.P. HARVEY: A cardiac pearl concerning syncope in a young person :teenage, 2Os, 30s) and most likely a female--be sure to consider and look for primary pulmonary hypertension. M.A. ENGLE~ My experience with children who had congenital heart disease is that the two chiefconditions associated with syncope are: (1) severe valvular aortic stenosis, which may have caused no recognized symptoms till the child starts to run fast and faints and (2) tetralogy of Fallot with "tet spells" or attacks ofparoxysmal dyspnea during which the baby turns more deeply cyanotic, anxious, and may lose consciousness! These episodes are attributed to sudden increase in spasm of the infundibular muscular hypertrophy in the outflow tract of the right ventricle, resulting in less pulmonary flow and greater right-to-left shunt with more hypoxia and then syncope. Propranolol relieves these episodes until surgery canbe carried out.

ACUTE

OR CHRONIC

NONCARDIAC

DISEASES

Several syndromes resulting from a galaxy of events may result in syncope, as illustrated by a patient with pain who reacts by hyperventilating with subsequent respiratory alkalosis and cerebral vasoconstriction. Depletion ofintravascular or extracellular volume due to diuretics or other losses may also result in ayncope. Bed rest in patients with chronic disease may result in altered autonomic tone. These individuals may experience syncope when they first attempt to ambulate, owing to a markedly deconditioned state. In a study of patients admitted to an intensive

care

unit

for

evaluation

of

syncope,

17%

(18

patients)

had

noncardiovascular causes: of these, 5 had neurologic diseases, 3 had pulmonary emboli, 4 had drug toxicity, 4 had orthostatic hypotension, and one each had vasovagal and posttussive syncope. Adetaileddiscussionofthenoncardiovascular causesofsyn37

cope is beyond memberthatthe multifold and

the

scope ofthis review,butit isimportantto recause ofsyncopein a particular patient maybe may require an elaborate diagnostic evaluation.

DRUGS

In the evaluation of patient with syncope, it is always important to consider the pertinent drugs that may contribute to the patient's symptoms. Antihypertensive drugs, including sympathetic blocking agents such as guanethidine, prazosin, captopril, may cause severe orthostatic hypotension, especially after the first dose. Diuretics often engender dizziness, weakness, and syncope by reducing the extracellular volume. Orthostatic hypotension occurs also with antipsychotic and antidepressant drugs, including phenothiazines, the tricyclic antidepressants, and MAO inhibitors. Any CNS depressant, including morphine, other narcotics, barbiturates,benzodiazepines, andthelike, may cause orthostatic hypotension and, in large doses, syncope. Alcohol is not only a CNS depressant but also may contribute to hypotensive symptoms by its vasodilator effect. Levodopa, a drug used fortreatmentofParkinson's disease, produces a mean reduction in the erect systolic blood pressure ofabout mm Hg and may produce syncope in susceptible individuals. Another mechanism by which drugs may precipitate syncope is by the production of arrhythmias. This is the case with the class I antiarrhythmic agents, such as quinidine, procainamide, and disopyramide. In these cases, as with large doses oftricyclic antidepressants, the syncopal episode could be produced by the occurrence of a polymorphic ventricular tachycardia called torsades de pointes, associated with the prolongation of the ECG QT interval (Fig 12).35 Other pharmacologic agents such as nicotine, caffeine, amphetamine, thyroid, and especially alcohol are important contributors to the onset of premature systoles that may produce disturbing symptoms, and also occasionally initiate sustained arrhythmias precipitating syncopal episodes. W.P.

HARVEY:

copal episodes prolapse had systolic click

Recently,1 was asked to see a patient who had 2 synwithin the past3 months. The possibility ofmitralvalve been considered even though no physician had detected a (or clicks) and/or a late apical systolic murmur. On evalpatient, he had no evidence of mitral valve prolapse. His

uation of the history, however, revealed that hypertension had been detected several months before. for which a diuretic had been m-escribed. I asked him when he last felt dizzy. He replied, “When I got -up from my chair in the waiting room to come in the office.” His blood pressure was then taken and it was 140/90 sitting and promptly fell to 98/50 on standing. This postural hypotensive effect was documented several times after this. He was taking twice to three times the usual dose of the diuretic used to control his hypertension which presumably resulted in hypotension 38

Fig 12.-Drug-induced quinidine-induced the lower tracing tiarrhythmic drugs certain patients.

and ment treat

torsacle de pointes, monitored strips. Upper tracing shows torsade; lower tracing shows procainamide-induced torsade. In a demand pacemaker has been implanted. The use of type I anmay aggravate the tendency to ventricular tachyarrhythmias in

syncope. His symptoms started after taking of his antihypertensive medication was his symptoms of dizziness and syncope.

PSYCHOLOGICAL

the the

diuretic. obvious

Adjustanswer to

FACTORS

Hyperventilation is commonly part of a symptom complex characteristic of an abnormal psychological mechanism accompanied by excessive anxiety, although it is frequently seen in emotionally stable patients. Another mechanism of syncope that is seen more frequently in emotionally unstable individuals is so-called vasovagal syncope. Syncope in these cases is the result of a decline in blood pressure mediated by excessive vagal stimulation. Syncope invariably occurs in the erect position and is frequently preceded by premonitory symptoms, such as weakness, nausea, sweating, and pallor. Psychogenic factors may precipitate arrhythmias in normal hearts as well as those with structural disease. Stimuli from the CNS affect both the sympathetic and parasympathetic autonomic systems, which under appropriate conditions may precipitate ectopic rhythms. Management of arrhythmias in these patients does not differ from management of psychologically stable patients, although arrhythmias in patients without evidence of heart disease are unlikely causes of syncope. DIAGNOSIS HISTORY to

AND

Among the the etiol.ogy

PH~SICAI,

EXAMINATION

many historical of the syncopal

features episode.

that those

may suggest referred to

the

a clue var39

ious circumstances temporally related to the loss of consciousness are especially important. Most syncopal episodes occur when the patient is in the upright position, and this posture is ofcourse a prerequisite for the diagnosis oforthostatic hypotension. The converse may be more valuable evidence,because syncope developing in a recumbent person considerably narrows the diagnostic possibilities. Shortage of energy substrates Chypoglycemia, hypoxia, alkalosis due to hyperventilation, etc.),tachyarrhythmias or bradyarrhythmias, and ventricular outflow obstruction (aortic stenosis, intracavitary tumors) may all result, in syncope in a seated or recumbent patient. Atria1 myxomas may result in transient loss of consciousness in a specific position, which might be upright or recumbent, or even lying on a specific side. Although most cases of postural syncope are assumed to be due to orthostatic hypotension, there are rare instances of syncope produced by postural heart block.36 Position may also play a role in carotid sinus hypersensitivity. In this case syncope may be precipitated by head tiliting or extension, shaving,or wearingtightcollars or ties. Insufficiency ofthe vertebrobasilar arterial system is animportantconsiderationinthe differential diagnosis in the case ofneurologic symptoms precipitated by head extension. A history ofdrug intake is extremely important in the patient with syncope, and questioning should cover use of antihypertensives, diuretics, tranquilizers, antidepressants, antipsychotics, antiparkinsonians, nitrates, digitalis preparations, and antiarrhythmics. The relation of syncope to meals (reactive hypoglycemia) or emotional stress (hyperventilation) may be important although nonspecific. The duration ofthe episode is relevant.Exceptfor cerebrovascular disease (where the episode is frequently preceded, accompanied by, or followed by focal neurologic signs), critical drops in cardiac output (global ischemia, aortic senosis, prolonged arrhythmias), and hypoglycemia,in whichthe episode may be prolonged, the duration of syncope rarely exceeds a few seconds. Symptoms such as yawning, faintness, nausea, and epigastric distress may precede the benign vasodepressor syncope. Hyperventilation may be suggested by paresthesias,muscletwitching, and dyspnea preceding the episode ofloss ofconsciousness. Syncope precipitated by exercise is a classic feature ofaortic stenosis, but tachyarrhythmias or myocardial ischemia may also be exercise related. Other symptoms such as palpitations, awareness of slow heart action, chest pain, neurologic disturbances, and personality changes may also offer clues to the diagnosis. The physical examination must be complemented by several simple maneuvers. To test for orthostatic hypotension, the supine blood pressureistakenfirstafierthe patient has been lying down for 5 minutes or more, and the measurement is repeated after the patient assumes the standing position. A consistent de40

crease of 30 mm Hg or more in the systolic pressure and a decrease of 15 mm Hg or more in the diastolic pressure are diagnostic, especially if the patient's symptoms are reproduced by the maneuver-In patients with true orthostatic hypotensionthe normal tachycardic response is not elicited on assuming the upright position. Ifthetachycardic response is not blunted, or even exaggerated, this is a sign that the orthostatic blood pressure changes are due to poor postural adjustment (abenign condition) or intravascular volume depletion secondary to losses or adrenal insufficiency. Performing the Valsalva maneuver (or cold pressor test) as described previously is also part ofthe evaluation of the integrity ofthe autonomic nervous system, as is questioning the patient about nausea, sweating, sexual habits, and urinary andbowelfunctionwhich when unaffected are signs ofanintact autonomic balance. A careful cardiac examination may confirm or rule out significant valvular disease such as aortic stenosis, mitral valve prolapse, and cardiomyopathies such as ASH. A murmur that changes with the position of the patient may be a clue of the presence ofanintracardiac myxoma. Palpation and auscultation of the carotids may direct the investigation toward hemodynamically significant left ventricular outflow obstruction or cerebrovascular disease. Palpation ofthe arterial pulse along with observation of the venous pulsations of the neck may offer valuable information about arrhythmias and the AV sequence of contractionCarotid sinus massage, performed after excluding the presence ofa carotid bruit,and always with ECG andblood pressure monitoring, may identify carotid sinus hypersensitivity if ventricular pauses of3 seconds or greater are recorded (cardioinhibitory type), or if there is a fall of 50 mm Hg or more in the systolic blood pressure (vasodepressor type) or of 30 mm Hg or more with associated cardiac slowing, and the patient's symptoms are reproduced (mixed type). ELECTROCARDIOGRAM The 1%lead ECG is an integral part of the evaluation of the patient with syncope, but its limitations have to be carefully considered. Most EGG clues are indirect and nondiagnostic and are valuable only to direct further diagnostic efforts toward the diagnoses suspected. Arrhythmias seen on ECG,Holtermonitoring, or event recording must be associated with symptoms to be ofdiagnostic significance. A prolonged QT interval is frequently associated with malignant polymorphous ventricular tachycardia ctorsades de pointes) (see Fig 12J,35 but the significance cf isolated ventricular premature beats on the ECG depends on the presence or absence of other ECG abnormalities, the hemody-

namic events produced by persistent early premature systoles incapable of adequate stroke volume (see Fig ll), as well as the patient's clinical status as far as presumed heart disease is concerned.'l Sinus bradycardia may be a norrnalfindingin athletes or elderly patients (see Fig l), but in other persons it may be a sign of sinus node dysfunction (see Fig 2).', Even sinus pauses and firstor second-degree AV block are not necessarily abnormal findings.8r14 The presence of "high-risk" bundle-branch blocks on the ECG of a patient evaluated for syncope is usually alarming, but the conduction system disease will progress in only a small percentage ofthese patients, and they tend not to suffer from recurrent syncope.'" LONG-TERM

ECG

MONITORING

The availability ofdevicesthatmonitorthe ECG continuously in ambulatory or hospitalized patients has enhanced our ability to detecttachyarrythmias and bradyarrhythmias in various settings, and some type of long-term monitoring is frequently necessaryin patients with syncope when no other obvious cause can be detected by simpler diagnostic procedures. The ability ofECG to detect arrhythmias in any particular case is a function ofthe time of monitoring. When the frequency of ventricular ectopy was evaluated with three consecutive 24-hour recordings in 15 patients,the spontaneous variation ofectopy frequency was 23% from day to day, 29% between S-hour periods within the same day, and 48% from hour to hour.37 Thus, longer monitoring periods are required to improve the chances ofrecording any specific event and to ensure that any changes are not due to spontaneous variation. The most important limitation of long-term ECG monitoring is that even if an event likely to produce a symptom such as syncope is recorded, there is no certainty that this event is responsible for the patient's symptoms in any particular case, although modern event recorders may help establish a temporal relationship between the symptoms and the presence or absence of a particular ECG event. As was mentioned earlier, the correlation between symptoms and arrhythmias on 24-hour recordings is poor; only 13% of 371 patients studied had concurrent symptoms and arrhythmias, whereas in 34% typical symptoms occurred without any arrhythmias that could be etiologically relatedtothose symptoms, and 86% ofpatients who hadtachycardias on the monitor record were asymptomatic at the time.'O Thus, the importance of establishing a firm temporal relationship between a syncopal episode and the corresponding ECG event potentially capable of producing syncope cannot be overemphasized.This is also trueforbradycardias,since, as we men42

tioned earlier, heart rates as low as 31 beats per minute and sinus pauses up to 2.81 seconds have been recorded in asymptomatic,healthy long-distance runners (see Fig l),with a 40% incidence oftype I second-degree AV block.* Resting heart rates of 50 beats per minute or lower are also found in more than 10% of asymptomatic elderly patients.9 The use of event recorders that can be activated by the patient has frequently established a temporal relationship between symptoms and a significant ar rhythmia. Hypertrophic cardiomyopathy is specifically associated with a high incidence of arrhythmia and syncope (see Fig 7). In patients with symptomatic hypertrophic cardiomyopathy, arrhythmias were found in 88% on long-term monitoring and were lifethreatening in 39YL2. All patients presented with syncope, presyncope, or palpitations. Pharmacologic suppression of the arrhythmias in these patients afforded marked symptomatic improvement, with elimination of the syncopal episodes, improvement in most patients ofthe other symptoms, and a decrease in the risk of sudden death.34 Another population in which long-term monitoring is likely to reveal the cause ofsyncope consists of patients with mitral valve prolapse, but here again the incidence of asymptomatic arrhythmias and uncorrelated symptoms is high."" EXERCISE TESTING, ECHOCARDIOGRAPHY,AND DTAGNOSTIC MOTIALITIES

OTHER

Exercise testing for arrhythmia detection is usually less rewarding than long-term monitoring, but it may be ofuse in patients with a history of exercise-related syncope. It must be remembered, however, that exercise testing is contraindicated in patients with clinical evidence of significant aortic stenosis. In other populations exercise testing may reveal arrhythmias related to ischemia, or hypotension due to decreased cardiac output in patients with dynamic outflow obstruction (hypertrophic cardiomyopathy), or marked left ventricular dysfunction in patients with multivessel coronary artery disease. Arrhythmias and/or hypotension may be responsible for the syncopal episodes. Echocardiography is presently the diagnostic standard for hypertrophic cardiomyopathy,mitralvalve prolapse,andmyxomas and may also offer some insightintothe problem ofarrhythmias related to left ventricular dysfunction and/or aneurysm formation in patients with ischemic heart disease or other forms of cardiomyopathy. In addition, echocardiography allows for a quantitative estimation ofthe degree ofleft ventricular dysfunction. Radionuclide ventriculography is also frequently used for LhiS purpose. 43

Noninvasive carotid flow studies or digital subtraction angiography are used for evaluation of patients with carotid bruits and cerebral symptoms. Electroencephalography, computed axial tomography, or cerebral angiography may sometimes be indicated in patients suspected of having seizures or brain lesions. Serum electrolyte determinations and glucose tolerance tests are indicated in patients with suspected extracellular volume disturbances or hypoglycemia. Serum hemoglobin determinations for suspected blood loss and cortisone or aldosterone assays to exclude primary and secondary adrenal abnormalities may be indicated in certain cases of orthostatic hypotension. Cardiac catheterization is almost universally indicated in patients with aortic stenosis who present with syncope. The transvalvular gradient is usually severe in these cases, warranting valvular replacement. ,&LA. ENGLE: In children with severe congenital valvular tises, the operation of choice is valvotomy rather than ment. The condition is thereby converted from severe Inild with none of the problems of an artificial valve.

aortic

&en-

valve replaceto moderate or

Syncope is a troubling clinical problem. The etiology may be completely benign, as in the poor postural adjustment found in young people, or it may be a precursor of sudden death, as in the case of malignant arrhythmia or heart block. Up to 19% of patients who die suddenly with ischemic heart disease report cerebral symptoms in the 2 weeks prior to their deathm3’ This alarming statistic, together with the fact that almost 50% of patients admitted for syncope remain undiagnosed at discharge,4 prompted the increased use over the last few years of invasive electrophysiologic techniques to evaluate patients with unexplained syncope. The basic study consists of the percutaneous insertion of several pacing and recording catheters at different intracardiac sites within the right atrium and ventricles for the purposes of (1) recording the sequence of activation of the heart during the patient’s own rhythm and with different stimulation techniques to identify AV bypass tracts that could explain the occurrence of supraventricular tachycardias; (2) recording the His bundle electrogram and measuring the conduction times between sinus node and AV node, within the AV node (AH interval), and below the AV node (HV interval), during the patient’s own rhythm and with atria1 stimulation; (3) recording the point at which AV block is produced during progressively faster atria1 pacing, and the site of the block inodal versus infranodali; (41 recording the blood pressure. preferably with an intra-arterial catheter during

the various pacing and stimulation procedures;(5) attempting to induce supraventricular and/or ventriculartachycardia with the technique of programmed electrical stimulation; (6) recording the atrial, AV nodal, and ventricular refractory periods; and (7) recording the chronotropic and blood pressure response to ca.rotid sinus stimulation during the patient's intrinsic rhythm andin different pacing modes. The abnormalities that may be potential causes ofsyncope include (1) rapid sustained ventricular or supraventricular tachyatria1 flutter, or fibrillation with rapid ventricular recardias, sponse, that reproduce the patient's presenting symptoms; (2) markedly prolonged recovery time of the sinus node after suppression ofthe sinus activity by overdrive pacing; (3) persistently prolonged refractory periods of the AV node; and (4) carotid sinus hypersensitivity, as defined earlier in this review, with reproduction of the patient's presenting sympt;oms. When pacing is needed for symptomatic control, the technique offers the additional advantage of providing a means to study which is the best pacing mode for each particular patient from the hemodynamic point of view. Also, when ventricular tachycardia is induced, acute and chronic drug testing with different antiarrhythmic agents for control of the tachycardia can be carried out. The indications for these studies remain controversial and are clearly limited to patients who experience recurrent unexplained syncope in spite of normal or equivocal results on noninvasive studies. This group includes the patients with incapacitating symptoms, those who work in potentially hazardous environments, such as individuals operating aircraft, dangerous machinery, or motor vehicles, survivors of unexplained sudden death,patients with abnormal rhythms on long-term monitoring and so on. The complicawithout correlation with symptoms, tions ofthe electrophysiologic study are similar to those ofother cardiac catheterization procedures. Electrophysiologic studies revealed a presumptive diagnosis in 17 of25 patients with recurrent syncope ofunknown cause after all other modalities failed to disclose a diagnosis. Therapy based on electrophysiologic findings provided complete symptomatic relief in 14 individuals during a mean follow-up of 1% years.3" Thus, thistechniqueis ofunquestionable value in some selected patients, although several reservations of these findings should. be noted: (1) There is only indirect evidence thattachyarrhythmists induced during programmed electrical stimulation WOK&. occur spontaneously and produce similar symptoms in any par. titular patient. Hence, the direct demonstration or absence o:-‘ the arrhythmia on an ECG recording at the time of a syncopa episode is far more specific than electrophysiologic testing. (2 jn patients with chronic bifascicular block Mthough syncopc 45

suggests progression to advanced or complete heart block, and a greatly prolonged infranodal conduction time (HV interval) has been considered an indirect evidencethatthisis likely to be the case,whenthese patients have been systematically studied, syncope tended not to recur. In fact, only 20% of these individuals had bradyarrhythmias that would have been amenable to pacing,whilethe risk ofsudden death was smallandno electrophysiologic variable was predictive of which patients were at increased risk.17,18 (3) A prolonged sinus node recovery time, although indicative ofsinus node dysfunction and potentially capable of producing symptoms in a patient with the brady-tachy syndrome followingthe abruptcessationoffast supraventricular rhythms, is not per se an indication that the spontaneously occurring syncopal episodes are due to sinus node disease. (4) Although treatment of patients with prolonged AV nodal refractoriness, even when this is reversed by atropine, had good results in some patients with syncope presumably due to hypervagatonia, this finding has been classical&y regarded as benign in patients without a history ofsyncope. MANAGEMENT

OF

THE

PATIENT

WITH

SYNCOPE

It is beyond the scope ofthis monograph to discuss the details of the management of the various pathologic entities that may manifest with syncope. The correct management plan depends on an accurate diagnosis, but, as we mentioned earlier, this is frequently not achieved: almost half of the patients with syncope admitted to an intensive care unit were discharged 9 days later, after extensive workup, without a definite diagnosis.* Fortunately, the syncopal episodes tended not to recur in these patients, making further investigation and therapy unnecessary. When there is clear evidence ofthe underlying etiologicalfactorthatprecipitated the syncopal episode, therapy should be directedto its correction. Patients with aortic stenosis who present with syncope will almost invariably have significant transvalvular gradients and need valve replacement. The surgical approach to intracardiac tumors producing enough hemodynamic impairment to result in syncope is usually successful. All drugs thatmayproduce syncope should be discontinuedbefore any further investigation is contemplated. This often includes class I antiarrhythmic agents (quinidine, disopyramide, procainamide) that may cause polymorphous ventricular tachycardia (see Fig 12).35 Patients with ischemic heart disease may experience syncope for a variety of reasons, and management will depend on the particular mechanism involved. In orthostatic hypotension, reversible causes must be corrected: blood loss and volume depletion, diuretics and hypotension-inducing drugs, and adrenal

insufficiency are all correctable. If the cause is not reversible, symptomatic measures are employed, generally with poor results. Elevating the head of the bed, slow tilting movements, exercise programswearing elasticized garments, and use ofvolume expanders, high-salt diets, and drugs like Sa-fluorohydrocortisone, vasopressors, and indomethacin have all been tried, with variable success; these methods should be tried in selected patients.'" Therapy for carotid sinus hypersensitivity depends onthetype of predominant disorder: vasodepressor versus cardioinhibitor. In patients with bradycardia during carotid sinus stimulation that reproduces the presenting syptomatology and is associated with a hypotensive response that is atleastpartially correctable by atropine administration or pacing, pacemaker therapy is indicated (see Fig 9).2s In patients with severe vasodepressor syncope, the ideal treatment remains to be established. Radiation therapy and surgical denervation ofthe carotid sinus have been attempted, with variable success. Finally, several remarks are in order on the treatment ofpatients with symptomaticbradyarrhythmias ortachyarrhythmias who present with syncope. In patients with the brady-tachy variety ofthe sick sinus syndrome, pharmacologictreatmentofthe tachycardias often depends on initial pacemaker control of the bradyarrhythmias, since most antiarrhythmic agents used to control supraventriculartachyarrhythmia would exacerbate the preexisting abnormal impulse formation and conduction. Pacemaker therapy for patients with bradyarrhythmias is indicated only when there is an unequivocal temporal relationship between symptoms and rhythm disturbances amenable to pacing since, as has been emphasized previously, arrhythmias without symptoms and symptoms without arrhythmias are frequent findings, and pacemaker therapy may not be of therapeutic value. o,32 Furthermore, inappropriate pacemaker management can exacerbate the patient's presenting symptoms by engendering one ofthe so-called pacemaker syndromes. These syndromes consistofdecreased cardiac output due to loss ofthe normal AV synchronism ofcontraction. Loss ofthe atrialcontributiontothe ventricular filling during ventricular pacing is only part of the problem. When there is intact ventriculoatrial conduction ofthe impulse, or in other cases of a closely synchronous atria1 contraction with abnormal opening of the AV valves during ventricular systole, regurgitation of blood into the atria and venous systems may occur.c Furthermore, newer dual-chamber and dual-mode pacemakers with blanking circuits can produce closed-looptachycardias due to retrograde conduction ofthe ventricular impulse to the atria. The medical profession in the United States has come under sharp criticism latel-y because of the implantation afwhat some 47

authorities consider too many pacemakers, especially when compared with other similarly developed countries such as England." This calls for special care in the selection ofpatients for pacemaker therapy and in the choice of the physiologic unit. This can be tested during the electrophysiologic studies or duringthe implantation ofthe definitive unit: a decrease of20 mm Hg of blood pressure with ventricular pacing usually signals a potential "pacemaker syndrome," in which case dual-chamber pacing is required; the rate and the AV interval of stimulation must be adjusted to achieve the best hemodynamic response in each particular case." Careful pharmacologic management of the tachyarrhythmias frequently requires electrophysiologic confirmation of efficacy (especially in life-threatening arrhythmias), and the clinician must consider the use of newer and sometimes less harmful methods of arrhythmia control, such as the "antitachycardia" pacemakersthatdetect andterminatethetachycardiaby underdrive or overdrive pacing, when pharmacologic therapy has failed to control the life-threateningtachycardias. Antitachycardia surgery is the last resort, especially in patients with left ventricular aneurysms. Electrophysiologic mapping of the ventricles and endocardial stripping ofthe areas responsible for the production ofthe arrhythmia atthetime ofthe aneurysmectomy is sometimes required to controlthetachycardia.40 Similar mapping techniques have been employed to identify and ablate by surgical or cryosurgical techniques accessory bypass tracts in patients with rapid symptomatic Wolff-Parkinson-White tachycardias. Prudent judgment and a mature clinical approach are required to identify and manage patients with syncope. Inappropriate use ofpowerfulvasoactive and chronotropic cardiac drugs as well as the introduction of complex circuitry dual-chamber pacemakers can frequently produce problems more symptomatic and more dangerous than the presenting pathologic process itself It has been the purpose ofthis review to emphasize a physiologic approach to the various clinical problems in these patients, thereby permitting the rational use ofthe diagnostic and therapeutic resources available. REFERENCES I 2.

Noble R.J.: Syncope. Car&ouasc. C&r. 12:119-130, 1981. Dreifus L.S.: Evaluation of svncone. dizziness and nalnitations: Cardiac vs. noncardiac causes, in Amsterdam-E:A. (ed.): Card& 1&zhemia and Arrh.ythmiss. Chicago, Year Book Medical Publishers, 1980, pp. 95-115. :I. Dermksian G., Lamb L.E.: Syncope in a population of healthy young adults: Incidence, mechanisms and significance. JAMA 168:1200-1207, 1958. 4. Silverstein M.D., Singer D.E., Mulley A.G., et al.: Patients with syncope admitted to medical intensive care units. JAMA 246:1185-1189, 1982. 48

5.

McIntosh

Am. 6. 7. 8. r,./. 10. 11. 12. 13.

H.D.,

Heart

J.

Estes

E.H.,

52:70--82,

Warren

J.V.:

The

mechanism

of

cough

syncope.

1956.

Dreifus L.S., Michelson E.L., Kaplinsky E.: Bradyarrhythmias: nificance and management. JACC, to be published. Major H.H.: Cdassic Descriptions of Disease. Oxford, England, entific Publications, 1948. Talan D.A., Baurenfeind R-A., Ashley W.W., et al.: Twenty-four uous ECG recordings in long-distance runners. Chest 82:X9-24, Camm A.J., Evans K.E., Ward D.E., et al: The rhythm nf the elderly subjects. Am. Heart J. 99:598603, 1980. Ferrer M.I.: The sick sinus syndrome. Circulation 47:635-641, Moss A.J., Davis R.J.: Brady-tachy syndrome. Prog. Cur-diouasc. 454, 1974. Narula O.S.: Atrioventricular conduction defects in patients dycardia. Circulation 44:1096-1110, 1971. Simonsen E., Straede N.J., Lyager N.B.: Sinus node dysfunction tients: A retrospective study with follow-up. Acta Med. Stand.

Clinical

sig-

Blackwell

Sci-

hour contin1982. heart in active 1973.

Dis. with

16:439--sinus in

bra128

pa-

208:343-348.

1980. 14

Meytes quent

I., Kaplinsky feat.ure following

E

, Yahini heavy

J-H., physical

et

al.: Wenckebach training. Am.

A-V

Heart

block:

J.

A

fre-

90:426-430.

1975. 7 -5 16.

17.

Dreifus L,.S.. Watanabe Y.: Localization and signrficance of atrioventricular block. Am. Heart J. 82:435-438, 1971. Rosenbaum M.B., Elizari M.V., Lazzari J.O.: The Hemiblocks. Oldsmar, Florida, Tampa Tracings, 1970. McAnulty J-H., Rahimtoola S.H., Murphy E., et al.: Natural history “high-risk” bundle branch block: Final report of a prospective study.

ET&. 18.

19.

20.

21. 22.

23.

24. 2s

26. 27. 28.

Dhingra fascicular tions. Hinkle bances

J.

Med. R.C., block:

307~137-143,

of N.

1982.

Denes P., Wu D., et al.: Syncope in patients with chronic biSignificance, causative mechanisms and clinical implicaAnn. Intern. Med. 81~302-306, 1974. L-E., Carver ST., Stevens M.: The frequency of asymptomatic disturof cardiac rhythm and conduction in middle-aged men. Am. J. Cardid. 24:629-650, 1969. Zeldis S.M., Levine B.J., Michelson E.L., et al.: Cardiovascular complaints: Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring. Chest 78:456-462, 1980. Desai D.C., Hershberg P.I., Alexander S.: Clinical significance of ventricular premature beats in an outpatient population. Chest 64:564-569, 1973. Follansbee W.P., Michelson E.L., Morganroth J.: Nonsustained ventricular tachycardia in ambulatory patients: Characteristics and association with sudden cardiac death. Ann. Intern. Med. 92:741-747, 1980. Mark A.L., Kioschos J.M., Abboud F.M., et al.: Abnormal vascular responses to exercise in patients with aortic stenosis. J. CEin. invest. 52:1138-1146, 1973. Schwartz L.S., Goldfischer J., Grover G.J., et al.: Syncope and sudden death in aortic stenosis. Am. J. Cardiol. 23:647-658, 1969. Liu H.Y., Panidis I., Soffer J., et al.: Echocardiographic diagnosis of intracardiac myxomas: Size, location and technical considerations, unpublished manuscript. Thomas J.E., Schirger A., Fealey R.D., et al.: Orthostatic hypotension. Mu.yo Clin. Proc. 56:117-125, 1981. Weiss S., Baker J.P.: The carotid sinus reflex in health and disease: Its role in causation of fainting and convulsions. Medicine 12:297-354, 1933. Franke H.: Uber das Karotidsinus-Syndrom und den sogenannten hyperak tzven Karotidsinus-RefZex. Stuttgart, Friedrich-Karl Schahauer-Verlag. ?96.3. p. 149

29. 30. 31.

32. 33. 34. ‘35. 36. 37. 38. 39. 40.

Morlel C-A., Perrins E.J., Grant P., et al.: Carotid sinus syncope treated by pacing: Analysis of persistent symptoms and role of atrioventricular sequential pacing. Br. Heart J. 47:411-418. 1982. Chadde K.D., Lichstein E., Gupta P.K., et al.: Bradycardia-hypotension syndrome in acute rnyocardial infarction: Reappraisal of the overdrive effects of atropine. Am. J. Med. 59:158-164, 1975. Chulze R-A., Strauss H.W., Pitt B.: Sudden death in the year following myocardial infarction: Relation to ventricular premature contractions in the late hospital phase and left ventricular ejection fraction. Am. J. &fed. 62:192199,1977. Winkle R.A., Lopes M.G., Fitzgerald J.W., et al.: Arrhythmias in patients with mitral valve prolapse. Circukztion 52173-81, 1975. DeMaria A.N., Amsterdam E-A., Vismara L-A., et al.: The variable spectrum of rhythm disturbances in the mitral valve prolapse syndrome, abstracted. CircUzation 49-5O(suppl. III):222, 1974. Canedo M.I., Frank M.J., Abdulla A.M.: Rhythm disturbances in hypertrophic cardiomyopathy: Prevalence, relation to symptoms and management. Am. J. Cardiol. 45:848-855, 1980. Soffer J., Dreifus L.S., Michelson E.L.: Polymorphous ventricular tachycardia associat.ed with normal and long QT intervals. Am. -I. Pardtol. 49:2021 2029, 1982. Seda P-E.. McAnultv J.H.. Anderson C.J.: Postural heart block. BT. Hew-f J. 443221-223, 1980. ” ’ Morganroth J., Michelson E.L., Horowitz L.N., et al.: Limitations of routine long~term electrocardiographic monitoring to assess ventricular ectopic frequency. Circulation 58:408-414, 1978. Kuller L., Cooper M., Perper J.: Epidemiology of sudden death. Arch. Intern. Med. 129:714-719, 1972. DiMarco J.P., Garan H., Harthorne J.W., et al.: intracardiac electrophysiologic techniques in recurrent syncope of unknown cause. Ann. Intern. Med. 95:542-548, 1981. Josephson M.E., Horowitz L.N.: Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia. Am. J. Cardiol. 43:631-642, 1979.

SELF-ASSESSMENT 1. 2. 3. 4. 5. 6. 7. 8.

b e c e e d e a, b. C’, d, e,

ANSWERS 9. e 10. e

11. e 12. 13. 14. 2 1, 3.4 S‘S 2. 3 -9

c e e