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1.  Physiological Phenomenology of Neurally-Mediated Syncope with Management Implications 
PLoS ONE  2011;6(10):e26489.
Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated (vasovagal) syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt –induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally-mediated syncope.
We studied 173 consecutive patients referred for unexplained syncope (114 women, 59 men, 42±1 years, 17±2 syncopal episodes). All had experienced (pre)syncope during head-up tilt testing followed by additional lower body negative suction. We classified hemodynamic responses according to the modified Vasovagal Syncope International Study (VASIS) classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa) or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the exact temporal relationship between hypotension and bradycardia to identify patients with true cardioinhibitory syncope.
Of the (pre)syncopal events during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II) progressively decreased from the youngest to the oldest age quartile. With more detailed temporal analysis, blood pressure reduction preceded the heart-rate decrease in all but six individuals (97%) overall and in 10 out of 11 patients with asystole (VASIS IIb).
Hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients, even in those classified as cardioinhibitory syncope according to the modified VASIS classification. Furthermore, cardioinhibitory syncope becomes less frequent with increasing age.
PMCID: PMC3201957  PMID: 22046292
2.  Clinical features of adenosine sensitive syncope and tilt induced vasovagal syncope 
Heart  2000;83(1):24-28.
AIM—To evaluate the possible relation between adenosine sensitive syncope and tilt induced vasovagal syncope.
METHODS—An ATP test and a head up tilt test were performed in 175 consecutive patients with syncope of uncertain origin. The ATP test consisted of the rapid intravenous injection of 20 mg of ATP; a positive response was defined as the induction of a ventricular pause (maximum RR interval) ⩾ 6000 ms. The head up tilt test was performed at 60° for 45 minutes; if negative, 0.4 mg oral glyceryl trinitrate spray was given and the test continued for a further 20 minutes; a positive response was defined as induction of syncope in the presence of bradycardia, hypotension, or both.
RESULTS—Of the 121 patients with a positive response, 77 (64%) had a positive head up tilt alone, 18 (15%) had a positive ATP test alone, and in 26 (21%) both ATP and head up tilt were positive. Compared with the patients with isolated positive head up tilt, those with isolated positive ATP were older (mean (SD) age, 68 (10) v 45 (20) years), had a lower median number of syncopal episodes (2 v 3), a shorter median duration of syncopal episodes (4 v 36 months), a lower prevalence of situational, vasovagal, or triggering factors (11% v 64%), a lower prevalence of warning symptoms (44% v 71%), and a higher prevalence of systemic hypertension (22% v 5%) and ECG abnormalities (28% v 9%). The patients with a positive response to both tests had intermediate features. Of the 44 positive responses to the ATP test, atrioventricular block was the cause of the ventricular pause in 43; of the 29 positive cardioinhibitory responses to head up tilt, sinus arrest was present in 23 cases and atrioventricular block in six.
CONCLUSIONS—ATP and head up tilt tests identify different populations of patients affected by syncope; these have different general clinical features, different histories of syncopal episodes, and different mechanism sites of action. Therefore, adenosine sensitive syncope and tilt induced vasovagal syncope are two distinct clinical entities.

Keywords: syncope; adenosine; ATP; head up tilt
PMCID: PMC1729251  PMID: 10618330
3.  Permanent pacing for cardioinhibitory malignant vasovagal syndrome. 
British Heart Journal  1994;71(3):274-281.
OBJECTIVE--To evaluate the effect of permanent pacing in cardioinhibitory malignant vasovagal syndrome. PATIENTS AND METHODS--37 patients with permanent pacemakers for cardioinhibitory malignant vasovagal syndrome. All presented with syncope (median six episodes, median frequency two episodes a year) and after conventional investigation and invasive electrophysiological assessment they remained undiagnosed, and without a generally accepted indication for pacemaker implantation. In all vasovagal syncope with cardioinhibition (heart rate at syncope < 60 beats/min) developed during tilt tests performed according to the Westminster protocol (head up tilt at 60 degrees with a footplate support for 45 minutes or until syncope intervenes). Dual chamber pacemakers were implanted in 35 (95%) and VVI pacemakers in the remaining two (5%). RESULTS--Over a mean (SD) follow up since implantation of 50.2 (23.9) months symptomatic improvement occurred in 89%: 62% remained free of syncope and 27% were completely symptom free. The collective syncopal burden of these 37 patients was reduced from 136 to 11 episodes each year. During follow up three patients died from unrelated causes. Patients who become asystolic during the tilt test (sinus pause of at least four seconds) experienced no greater benefit from pacing than those with less extreme cardioinhibition. Patients who remained free of syncope since implantation were younger than those who continued to experience syncope. Patients who remained completely symptom free after implantation were younger, more likely to be male, and had had fewer syncopal episodes before implantation than those who continued to experience syncope or presyncope. No other demographic, clinical, investigative, or pacing variable suggested a more favourable outcome after implant. CONCLUSIONS--This retrospective and uncontrolled experience suggests a possible role for permanent pacing in selected patients with cardioinhibitory malignant vasovagal syndrome. Improved acquisition of tilt test data may enable better selection of patients who are suitable for permanent pacing. A randomised prospective study to compare permanent pacing with no treatment or with medical treatment in cardioinhibitory malignant vasovagal syndrome is indicated.
PMCID: PMC483666  PMID: 8142198
4.  Effect of patient characteristics on the yield of prolonged baseline head-up tilt testing and the additional yield of drug provocation. 
Heart  1996;76(5):406-411.
OBJECTIVE: To define the value of tilt testing and hte additional yield of drug provocation over prolonged baseline tilt in different patient subgroups. (Many different protocols are in use for head-up tilt testing in heterogeneous groups of patients. Not all patients in reported series have recurrent syncope, and there is often a wide age range and a variable incidence of structural heart disease.) DESIGN: In a prospective study, baseline 60 degrees head-up tilt testing was undertaken for 45 minutes, initially without drug provocation. Patients who remained symptom free were given intravenous isoprenaline (isoproterenol) and further tilting or edrophonium (10 mg bolus) during tilt, in an order determined randomly before the start of the test. If they were symptom free after the first drug, they were given the other drug. A positive test was recorded when syncope or pre-syncope occurred with a rapid fall (> 30%) in blood pressure. The impact on tilt result of the type of symptoms, presence of significant structural heart disease (SHD), presence of a non-cardiovascular cause of sudden diminished consciousness (SDC), and age was then assessed by subgroup analysis. PATIENTS: 145 patients (73 female, mean age 51 (25), range 8-94) with one or more episodes of pre-syncope or syncope. RESULTS: 39 patients (27%, 21 female, age 49 (25) years) had positive tests and 106 (73%, 52 female, age 52 (25) years) negative tests. 27 (69%) had a positive test during baseline tilt at 20.5 (10.8) minutes, five (13%) with isoprenaline infusion, and seven (18%) with edrophonium bolus. Patients with recurrent syncope rather than single syncopal episodes or single or recurrent pre-syncope were more likely to have a positive tilt test (41% v 17%, P < 0.005) and patients with SHD or SDC (69/14 patients) were much less likely than patients without (16% v 42%, P < 0.0001). The yield of positive tests was similar if patients were below (26%) or above (27%) the mean age (50 years). When multiple factors were combined, the yield ranged from 0% for 21 patients under 50 years with SHD or SDC and without recurrent syncope to 73% in 11 patients over 50 years with recurrent syncope and no SHD or SDC. The additional yield in subgroups over 45 minute baseline tilt (70 (11)%) of isoprenaline (13 (10)%) was similar to that of edrophonium (17 (8)%, P = NS), but six (50% of those who were drug positive) patients required a second drug to produce a positive result (two with isoprenaline second, four with edrophonium second). CONCLUSIONS: Head-up tilt testing in a heterogeneous population has a low yield. Simple clinical characteristics define the type of patient who is likely to have a positive tilt test and the patient who is not and in whom other investigations should receive priority. The great majority of positive tests will occur during prolonged baseline testing if this is used. Isoprenaline and edrophonium produced similar additional yields of positive tests.
PMCID: PMC484570  PMID: 8963892
5.  Epidemiology of Syncope in Hospitalized Patients 
To describe the etiologies of syncope in hospitalized patients and determine the factors that influence survival after discharge.
Observational retrospective cohort.
Department of Veterans Affairs hospital, group-model HMO, and Medicare population in Oregon.
Hospitalized individuals (n = 1,516; mean age ± SD, 73.0 ± 13.4 years) with an admission or discharge diagnosis of syncope (ICD-9-CM 780.2) during 1992, 1993, or 1994.
During a median hospital stay of 3 days, most individuals received an electrocardiogram (97%) and prolonged electrocardiographic monitoring (90%), but few underwent electrophysiology testing (2%) or tilt-table testing (0.7%). The treating clinicians identified cardiovascular causes of syncope in 19% of individuals and noncardiovascular causes in 40%. The remaining 42% of individuals were discharged with unexplained syncope. Complete heart block (2.4%) and ventricular tachycardia (2.3%) were rarely identified as the cause of syncope. Pacemakers were implanted in 28% of the patients with cardiovascular syncope and 0.4% of the others. No patient received an implantable defibrillator. All-cause mortality ± SE was 1.1%± 0.3% during the admission, 13%± 1% at 1 year, and 41%± 2% at 4 years. The adjusted relative risk (RR) of dying for individuals with cardiovascular syncope (RR 1.18; 95% confidence interval [CI] 0.92, 1.50) did not differ from that for unexplained syncope (RR 1.0) and noncardiovascular syncope (RR 0.94; 95% CI 0.77, 1.16).
Among these elderly patients hospitalized with syncope, noncardiovascular causes were twice as common as cardiovascular causes. Because survival was not related to the cause of syncope, clinicians cannot be reassured that hospitalized elderly patients with noncardiovascular and unexplained syncope will have excellent outcomes.
PMCID: PMC1496762  PMID: 10571716
syncope; prognosis; mortality
6.  Swallow syncope associated with complete atrioventricular block and vasovagal syncope 
Heart  2000;83(6):702-704.
A 21 year old man presented with multiple, recurrent episodes of complete atrioventricular (AV) block associated with swallowing. Electrophysiological study revealed an AV block with swallowing of carbonated beverages and balloon inflation in the lower oesophagus. Evaluation did not demonstrate any underlying oesophageal or cardiac disease, and the AV block was not induced after intravenous atropine administration. The AV block was probably caused by a hypersensitive vagotonic reflex triggered by mechanical receptors in the lower oesophagus, resulting in suppression of the AV node. Head up tilt test revealed an increase in the high frequency spectrum of heart rate variability before the onset of the syncope. These findings suggest that the amplitude of the continual fluctuations in response to a variety of stimuli and derangement from both intrinsic and extrinsic environments was greater in this patient than in normal subjects. Swallow syncope is an unusual but treatable disorder. These reflexes that become exaggerated to the point of causing illness are poorly understood.

Keywords: swallow syncope; AV block; electrophysiological study; head up tilt test
PMCID: PMC1760849  PMID: 10814634
7.  The Artificial Cardiac Pacemaker—Indications for Implantation 
California Medicine  1964;101(6):422-426.
Extensive clinical experience has demonstrated that implantable cardiac pacemakers are safe and effective mechanisms for controlling symptoms and preventing the hazards of third degree heart block with Stokes-Adams syncope. Medical management of this disease does not provide reliable protection and life expectancy averages about two years after diagnosis. Hence the negligible surgical morbidity and mortality associated with pacemaker implantation justifies broad indications to implant one of the four commercially available battery-powered units.
Elective implantation of a pacemaker should be considered in patients with persistent third degree heart block who have had: One or more episodes of Stokes-Adams syncope; surgical injury to the conduction system, regardless of syncopal attacks; evidence of low cardiac output with cardiomegaly secondary to bradycardia. Few if any other cardiac arrythmias are satisfactorily controlled by an electrical pacemaker.
Emergency pacemaker control is obviously necessary for patients developing intractable or recurrent bouts of asystole. During the interval until an implantable unit can be obtained and sterilized, the patient may be controlled by intravenous isoproterenol or by an external pacemaker attached to a transvenous catheter electrode, a precordial skin electrode or a percutaneous myocardial wire electrode.
PMCID: PMC1515862  PMID: 14236028
8.  Intermittent Brugada Syndrome Presenting with Syncope in an Adult Female 
Background. Brugada syndrome accounts for 4–12% of all sudden deaths worldwide and at least 20% of sudden deaths in patients with structurally normal hearts. Case Report. A 48-year-old female presented to the emergency department after two witnessed syncopal episodes. While awaiting discharge had a third collapse followed by cardiac arrest with shockable rhythm. Initial electrocardiogram showed wide QRS complex with left axis deviation, ST-segment elevation of <1 mm in V1 and V2, and flattening of T waves in V1. The angiogram did not demonstrate obstructive coronary disease. The electrocardiogram obtained two days after these events showed a right bundle branch block with ST-segment elevation of >2 mm followed by a negative T wave with no isoelectric separation, suggestive of spontaneous intermittent Brugada type 1 pattern. Cardiac magnetic resonance imaging demonstrated neither structural heart disease nor abnormal myocardium. After placement of an implantable cardioverter defibrillator the patient was discharged. Why should an emergency physician be aware of this? Brugada syndrome is an infrequently encountered clinical entity which may have a fatal outcome. This syndrome primarily presents with syncope. It should be considered as a component of differential diagnosis in patients with family history of syncope and sudden cardiac death.
PMCID: PMC4211173  PMID: 25371832
9.  Long-Term Electrical Stimulation of the Heart in Stokes-Adams Disease 
Ten patients, between the ages of 39 and 75 years, underwent subcutaneous implantation of an electrode pacemaker for relief of recurrent syncopal episodes of Stokes-Adams disease. Their prolonged course of severe disability on medical therapy is in marked contrast to their new life, free of syncopal attacks, on pacemaker therapy. Experience in the management of these patients has shown that the electrode catheter, introduced intravenously to stimulate the right ventricular endocardium, is the best temporary therapy in a patient with uncontrollable syncopal attacks, and it should be used in all patients undergoing the surgical procedure of implantation. Pacemaker therapy is applicable to patients in sinus rhythm as well as to those in complete heart block. Observations on the effect of heart rate on cardiac output have shown the need of a faster rate in the presence of congestive failure for the maintenance of an adequate cardiac output. The favourable course of patients after implantation of a pacemaker indicates that this is the treatment of choice in Stokes-Adams disease.
PMCID: PMC1922003  PMID: 14055828
10.  Midodrine: a role in the management of neurocardiogenic syncope 
Heart  1998;79(1):45-49.
Objective—To determine the benefit of midodrine, an α agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope.
Setting—Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope).
Patients—16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt.
Design and intervention—Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation.
Results—Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4 ). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo ( p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects.
Conclusions—Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms.

 Keywords: midodrine;  neurocardiogenic syncope;  head up tilt test
PMCID: PMC1728578  PMID: 9505918
11.  Progressive Familial Heart Block Type I in a Korean Patient 
Korean Circulation Journal  2011;41(5):276-279.
A 29-year-old man was referred to the emergency department with a complaint of abdominal pain and dizziness. He had experienced two previous syncopal episodes. His family history revealed that his mother and his two uncles had received permanent pacemaker implantation. His initial heart rate was 49 beats per minute. The electrocardiography (ECG) showed atrial flutter and right bundle branch block (RBBB) with left anterior fascicular block (LAFB). On admission, 24-hour Holter showed ventricular pause up to 16 seconds during syncope. Radio frequency catheter ablation (RFCA) of atrial flutter was performed. The ECG revealed bifascicular block (RBBB and LAFB) and first-degree atrioventricular block. He received a permanent pacemaker implantation. His brother's and his sister's ECGs also showed trifascicular block and the pedigree showed autosomal dominant inheritance. This patient was diagnosed with a progressive familial heart block (PFHB) type I. This would be the first report of a PFHB type I case documented in Korea.
PMCID: PMC3116107  PMID: 21731570
Hereditary bundle branch system defect; Atrial flutter
12.  Cerebral blood flow during vasovagal syncope induced by active standing or head up tilt 
Sung, R | Du Z, D | Yu, C | Yam, M | Fok, T
Archives of Disease in Childhood  2000;82(2):154-158.
BACKGROUND—Vasovagal syncope is usually associated with a sudden drop of blood pressure and/or heart rate. However, occasionally the symptoms of syncope induced by orthostatic stress testing are not associated with obvious haemodynamic changes. The mechanisms of syncope in these patients are not clear.
AIM—To evaluate changes in cerebral blood flow velocities during orthostatic stress testing in children and adolescents with vasovagal syncope.
METHODS—Electrocardiogram, instantaneous arterial blood pressure, and right middle cerebral artery blood flow velocity were recorded at rest, during active standing, and 80° head up tilt. 32 children and adolescents aged between 7 and 18 years with a history of repeated vasovagal syncope and 23 healthy control subjects were studied.
RESULTS—Presyncope occurred in 10 patients during standing, and 13 patients during head up tilt. None of the controls had symptoms during the test. The transcranial Doppler study showed that the symptoms were associated with significant decreases of diastolic cerebral blood flow velocity and an increase of pulsatility. There was no significant change of the systolic cerebral blood flow velocity. The changes of cerebral blood flow velocities occurred in all episodes of presyncope, including those not associated with severe drop of blood pressure or heart rate.
CONCLUSIONS—Diastolic cerebral blood flow velocity decreased significantly during episodes of presyncope induced by orthostatic stress. Impairment of autoregulation of cerebral blood flow might play an important role in the pathophysiology of syncope.

PMCID: PMC1718216  PMID: 10648373
13.  Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. 
Journal of Clinical Investigation  1997;99(11):2736-2744.
The pathophysiology of neurally mediated syncope is poorly understood. It has been widely assumed that excessive sympathetic activation in a setting of left ventricular hypovolemia stimulates ventricular afferents that trigger hypotension and bradycardia. We tested this hypothesis by determining if excessive sympathetic activation precedes development of neurally mediated syncope, and if this correlates with alterations in baroreflex function. We studied the changes in intraarterial blood pressure (BP), heart rate (HR), central venous pressure (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked by upright tilt in recurrent neurally mediated syncope patients (SYN, 5+/-1 episodes/mo, n = 14), age- and sex-matched controls (CON, n = 23), and in healthy subjects who consistently experienced syncope during tilt (FS+, n = 20). Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were obtained after infusions of phenylephrine and sodium nitroprusside. Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope. SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing. FS+ subjects had the largest decrease in CVP with tilt and had significant increases in MSNA and heart rate baroreflex slopes. These data challenge the view that excessive generalized sympathetic activation is the precursor of the hemodynamic abnormality underlying recurrent neurally mediated syncope.
PMCID: PMC508120  PMID: 9169504
14.  Post-micturitional hypotension in patients with multiple system atrophy 
Background: Patients with multiple system atrophy (MSA) occasionally have episodes of syncope or pre-syncope after micturition.
Objective: To clarify the mechanism of these episodes by investigating the haemodynamic changes associated with micturition.
Methods: 25 patients with probable MSA and 16 age matched normal controls were studied. Continuous records of blood pressure and heart rate were made during water cystometry, along with the Valsalva manoeuvre, head up tilt testing, measurement of plasma noradrenaline, and calculation of coefficient of variance of RR intervals.
Results: Compared with normal controls, MSA patients had a lower baseline blood pressure, smaller blood pressure and heart rate increases during bladder filling, and an abnormal fall in blood pressure for a longer duration after voiding, resulting in significantly lower blood pressure than at baseline (mean systolic blood pressure reduction –15.2 mm Hg), and hypotension compared with control blood pressure (–29.0 mm Hg). The blood pressure fall was greater in patients with micturition syncope/pre-syncope than in those without. It was also greater in patients with abdominal straining resulting from difficulty in voiding. Other cardiovascular indices did not correlate with the fall in blood pressure.
Conclusions: Hypotension after voiding in MSA patients may result from generalised autonomic dysfunction and abnormal abdominal straining, resulting in micturition syncope.
PMCID: PMC1739492  PMID: 15654029
15.  Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus 
Texas Heart Institute Journal  2002;29(1):37-39.
A 41-year-old man with no relevant cardiac history presented for evaluation of episodic syncope. Electrocardiography showed sinus rhythm with right bundle-branch block and Q waves in leads II, III, and aVF. Subsequent exercise treadmill testing and technetium 99m sestamibi study revealed a reversible posterior defect. Coronary angiography later showed a right coronary artery that arose from the left coronary sinus—an anomaly that has been associated with angina, myocardial infarction, and sudden cardiac death.
After being informed of the potential risks and options associated with this anomaly, the patient chose long-term β-blocker medical therapy. At follow-up, this treatment appeared to have resolved his episodic syncope. (Tex Heart Inst J 2002;29:37–9)
PMCID: PMC101267  PMID: 11995848
Coronary vessel anomalies/diagnosis/complications/pathology/therapy; heart catheterization; risk assessment
16.  Recurrent Syncope Episodes and Exercise Intolerance in Hypertrophic Cardiomyopathy Combined with Atrioventricular Conduction Disturbance 
A 30-year-old female patient with known hypertrophic cardiomyopathy (HCMP) was admitted for recurrent syncope episodes. Electrocardiogram (ECG) showed 2 : 1 atrioventricular (AV) block. Stress echocardiography with bicycle showed high grade AV block at high stage of the exercise associated with exercise intolerance and dyspnea. Twenty-four hour ECG monitoring also revealed high grade AV block and 1 episode of non-sustained ventricular tachycardia. Implantable cardioverter/defibrillator-pacemaker (ICD-P) was inserted. After implantation of ICD-P, conduction disturbance and exercise intolerance were improved. AV block is a rare complication HCMP. There are just a few case reports that present symptoms caused by conduction disturbance in HCMP. This case describes repeated syncope episodes and exercise intolerance caused by conduction disturbance during exercise in HCMP patient. For evaluating the cause of syncope in HCMP, stress echocardiography can be helpful to understand the probable mechanism of syncope.
PMCID: PMC3816167  PMID: 24198923
Hypertrophic cardiomyopathy; Syncope; Atrioventricular block; Stress echocardiography
17.  Complete heart block. Studies of atrial and ventricular pacemaker site and function. 
British Heart Journal  1975;37(11):1156-1160.
Atrial and ventricular pacemaker function was studied in 20 patients with idiopathic chronic complete heart block using the rate response to an intravenous bolus dose of isoprenaline (5 mug/70 kg bodyweight). Pacemaker responses were compared with those of 16 normal control subjects. None of the patients was having syncopal attacks at the time of admission and they were therefore selected in that none required immediate pacing. Ten of the patients had His bundle electrograms; all were shown to have a pre-His type of atrioventricular block. Two major groups emerge from the responses to isoprenaline. (a) High risk group: 11 of the 14 patients with reduced ventricular pacemaker responses had frequent syncopal attacks; 8 of the patients with Adams-Stokes syncope had a bundle-branch block pattern, while 3 had a narrow QRS. These patients require pacing. (b) Low risk group: a low risk asymptomatic group (5 patients) was identified with atrial and ventricular responses to isoprenaline within normal range. One of these patients had a bundle-branch block pattern, while 4 had a narrow QRS. These patients might be managed without pacing. The atrial response to isoprenaline was reduced in 12 of the 20 cases, 10 of whom also had reduced ventricular responses. All 9 patients with bundle-branch block had reduced ventricular responses, while 7 had reduced atrial responses. This evidence indicates that cardiac conducting tissue pathophysiology is widespread in complete heart bolck. The present work suggests that consideration of the ventricular pacemaker function is important in assessing liability to syncope in complete heart block. While patients with Adams-Stokes attacks require pacing it is suggested that all asymptomatic patients with complete heart block and those with minor symptoms are assessed using studies of both ventricular pacemaker function and site. A low risk group not requiring a pacemaker may emerge after sufficient follow-up assessment.
PMCID: PMC482933  PMID: 1191431
18.  Exercise-Induced Vasodepressor Syncope in a Collegiate Wrestler: A Case Study 
Journal of Athletic Training  1997;32(4):359-362.
To present the case of an 18-year-old collegiate wrestler diagnosed with vasodepressor syncope.
Vasodepressor syncope and the pathophysiologic mechanisms responsible are not fully understood. It is postulated that a sudden, rapid reduction in venous return to the heart allows for quite forceful ventricular contractions. Hypotension, bradycardia, and possible cerebral hypoxia may result, which could cause loss of consciousness.
Differential Diagnosis:
Cardiovascular, neurologic, metabolic, and psychogenic causes.
Pharmacologic therapy of fludrocortisone acetate and potassium chloride was effective. The athlete returned to full activity without restrictions and remained symptom free throughout the remainder of the season.
Vasodepressor syncope is usually associated with full syncope. However, this 18-year-old wrestler never fully lost consciousness. His symptoms occurred primarily with exercise.
The athletic trainer should consider exercise- induced vasodepressor syncope as a possible etiology for those athletes who present with presyncopal episodes.
PMCID: PMC1320355  PMID: 16558473
presyncope; tilt-table test; cardiovascular system; cerebral hypoxia
19.  Permanent cardiac pacing for neurocardiogenic syncope 
Netherlands Heart Journal  2008;16(Suppl 1):S15-S19.
Vasovagal syncope is not a benign condition in the elderly population. In patients not responsive to conservative therapy and whose abrupt faints are associated with serious injuries and seriously affected quality of life, pacemaker therapy was suggested. However, the usefulness of cardiac pacing for the prevention of recurrences of vasovagal syncope remains controversial because of the dominant role of the vasodepressor component during the episode. In the Medical Center Alkmaar, the Head-Up Tilt Test (HUTT) has been used since 1996 during the work-up of patients who present with vasovagal syncope. The HUTT showed a dominant cardioinhibitory response in 4.5% of our patients; in elderly patients with vasovagal syncope without prodromal symptoms and refractory on conservative therapy, pacemaker therapy was very effective in preventing syncope during long-term follow-up. (Neth Heart J 2008;16(Suppl1):S15-S19.)
PMCID: PMC2572013  PMID: 18958263
vasovagal; syncope; cardiac; pacing
20.  Intravenous fentanyl during shoulder arthroscopic surgery in the sitting position after interscalene block increases the incidence of episodes of bradycardia hypotension 
Korean Journal of Anesthesiology  2011;60(5):344-350.
Episodes of bradycardia hypotension (BH) or vasovagal syncope have a reported incidence of 13-29% during arthroscopic shoulder surgery in the sitting position after an interscalene block (ISB). This study was designed to investigate whether intravenous fentanyl during shoulder arthroscopy in the sitting position after ISB would increase or worsen the incidence of BH episodes.
In this prospective study, 20 minutes after being in a sitting position, 160 patients who underwent ISB were randomized to receive saline (S, n = 40), 50 µg of fentanyl (F-50, n = 40), 100 µg of fentanyl (F-100, n = 40) or 30 mg of ketorolac (K-30, n = 40) randomly. We assessed the incidence of BH episodes during the operation and the degree of maximal reduction (Rmax) of blood pressure (BP) and heart rate (HR).
The incidence of BH episodes was 10%, 15%, 27.5% and 5% in the S, F-50, F-100 and K-30 groups, respectively. Mean Rmax of systolic BP in the F-100 group was significantly decreased as compared to the S group (-20.0 ± 4.5 versus -6.3 ± 1.6%, P = 0.004). Similarly, mean Rmax of diastolic BP in the F-100 group was also significantly decreased (P = 0.008) as compared to the S group.
These results suggest that fentanyl can increase the incidence of BH episodes during shoulder arthroscopic surgery in the sitting position after ISB.
PMCID: PMC3110293  PMID: 21716907
Bradycardia; Fentanyl; Hypotension; Interscalene block; Vasovagal syncope
21.  Gender Difference in Patients with Recurrent Neurally Mediated Syncope 
Yonsei Medical Journal  2010;51(4):499-503.
The gender difference of neurally mediated syncope is not well defined in a large patient population. The aim of this study was to evaluate the gender difference of clinical manifestations in patients with neurally mediated syncope who underwent head-up tilt test.
Materials and Methods
The medical records of 1,051 consecutive patients with two or more episodes of syncope, who were diagnosed as having neurally mediated syncope by head-up tilt test, were retrospectively reviewed.
Of 1,051 patients, 497 (47.3%) patients were male and 554 (52.7%) patients were female. Female patients were experiencing syncopal episodes for longer periods of their lives (8.2 ± 9.5 years vs. 6.8 ± 9.2 years, p = 0.002) and more episodes of syncope prior to head-up tilt test (HUT) (7.2 ± 9.4 vs. 5.0 ± 6.4, p = 0.001) than male patients. Micturition syncope (20.0% vs. 5.2%, p < 0.001) was observed more frequently in male patients than in female patients. To the contrary, however, defecation syncope (16.3% vs. 9.3%, p < 0.001) was observed more frequently in female patients than in male patients.
Female patients were experiencing syncopal episodes for longer periods of their lives and more episodes of syncope than male patients. Gender difference was also noted with regard to frequency of situational syncope.
PMCID: PMC2880260  PMID: 20499413
Neurally mediated syncope; sex difference
22.  Prevalence and Clinical Factors of Anxiety and Depression in Neurally Mediated and Unexplained Syncope 
Yonsei Medical Journal  2013;54(3):583-589.
Several studies have demonstrated that psychiatric disorders such as anxiety, depression and panic attack are associated with syncope, especially vasovagal and unexplained syncope (US). The aim of this study was to compare the prevalence of anxiety and depression between patients with neurally mediated syncope (NMS) and US and to investigate the clinical factors associated with anxiety and depression.
Materials and Methods
Between January 2009 and March 2010, 383 patients with syncopal episodes completed a Hospital Anxiety and Depression Scale questionnaire to assess symptoms of anxiety and depression. Inclusion criteria were NMS and US. Exclusion criteria were cardiac syncope, orthostatic hypotension and other disorders mimicking syncope. After exclusion, 199 patients were included.
There were 176 (88.4%) NMS patients and 23 (11.6%) US patients. The prevalence of abnormal anxiety and depression were not significantly different between the NMS and US groups (10.2% vs. 8.7%, p=0.99; 8.5% vs. 17.4%, p=0.24). Clinical factors associated with anxiety were female gender (p=0.01) and six or more recurrent syncopal episodes (p=0.01) by univariate analysis. The only factor associated with abnormal anxiety score (OR=20.26, 95% CI: 1.4-291.6, p=0.01) was more than six recurrent syncopal episodes, while a positive head-up tilt table testing response was inversely associated with abnormal depression score (OR=0.28, CI: 0.08-0.97, p=0.04) in the multiple logistic regression analysis.
Anxiety was associated with frequent syncopal episodes. Thus, anxiety might be considered in the management of syncope patients.
PMCID: PMC3635653  PMID: 23549800
Anxiety; depression; syncope
23.  Autonomic Dysfunction Presenting as Postural Orthostatic Tachycardia Syndrome in Patients with Multiple Sclerosis 
Background: Autonomic dysfunction is common in patients suffering from multiple sclerosis (MS) and orthostatic dizziness occurs in almost 50% of these patients. However, there have been no reports on postural orthostatic tachycardia syndrome (POTS) in patients suffering from MS.
Methods: The patients were included for analysis in this study if they had POTS with either a prior history of MS or having developed MS while being followed for POTS. Postural orthostatic tachycardia (POTS) is defined as symptoms of orthostatic intolerance(>6months) accompanied by a heart rate increase of at least 30 beats/min (or a rate that exceeds 120 beats/min) that occurs in the first 10 minutes of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. We identified nine patients with POTS who were suffering from MS as well. Each of these patients had been referred from various other centers for second opinions.
Results: The mean age at the time of diagnosis of POTS was 49±9 years and eight of the 9 patients were women. Five patients (55%) had hyperlipidemia, 3 (33%) migraine and 2 (22%) patients had coronary artery disease and diabetes each. Fatigue and palpitations (on assuming upright posture) were the most common finding in our patients (9/9). All patients also had orthostatic dizziness. Syncope was seen in 5/9(55%) of patients. Four patients (44%), who did not have clear syncope, were having episodes of near syncope. The presence of POTS in our study population resulted in substantial limitation of daily activities. Following recognition and treatment of POTS, 6/9(66%), patients were able to resume daily activities of living. Their symptoms (especially fatigue and orthostatic intolerance) improved. The frequency and severity of syncope also improved. Three (33%) patients failed to show a good response to treatment.
Conclusion: Patients suffering from MS may manifest autonomic dysfunction by developing POTS. Early recognition and proper management may help improve the symptoms of POTS.
PMCID: PMC2840604  PMID: 20309394
Multiple sclerosis; Postural tachycardia syndrome; syncope; dizziness; fatigue.
24.  Risk Factors for Recurrent Syncope and Subsequent Fatal or Near-Fatal Events in Children and Adolescents with Long QT Syndrome 
We aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS).
Data regarding risk assessment in LQTS after the occurrence of first syncope are limited.
The Prentice-Williams-Peterson conditional gap time model was utilized to identify risk factors for recurrent syncope from birth through age 20 years among 1648 patients from the International LQTS Registry.
Multivariate analysis demonstrated that QTc duration (≥500 msec) was a significant predictor of a first syncope (HR=2.16), whereas QTc effect was attenuated when the endpoints of second-, third-, and fourth- syncope were evaluated (HR = 1.29, 0.99, 0.90, respectively; p<0.001 for the null hypothesis that all four HRs are identical). A genotype-specific sub-analysis showed that during childhood (0–12 years) LQT1 males had the highest rate of first syncope (p=0.001), but exhibited similar rates of subsequent events as other genotype-gender subsets (p=0.63). In contrast, in the age-range of 13–20 years, LQT2 females experienced the highest rate of both first and subsequent events (p<0.001 and p=0.01, respectively). Patients who experienced ≥1 episodes of syncope had a 6–12-fold (p<0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events.
Children and adolescents who present following an episode of syncope should be considered to be at a high a risk for the development of subsequent syncopal episodes and fatal/near-fatal events regardless of QTc duration.
PMCID: PMC3052409  PMID: 21329841
long qt syndrome; corrected QT interval; reccurrent events; syncope; sudden cardiac death
25.  Ambulatory electrocardiographic records in patients with transient cerebral attacks or palpitation. 
British Medical Journal  1975;4(5996):569-571.
Continuous electrocardiographic (ECG) records were made over 24 hours in 130 ambulant outpatients complaining of syncope, dizzy turns, or palpitation. In all these patients resting ECGs had failed to show significant dysrhythmias. Exercise testing was performed on 64 patients and also failed to reveal any dysrhythmias. Analysis of the tape recordings, however, showed appreciable dysrhythmias in 74% of the group. In most cases the dysrhythmias were complex mixtures of rapid supraventricular and ventricular rhythms. bouts of ventricular tachycardia were seen in seven patients, all of whom were women. Episodic complete heart block was seen in only two patients, but prolonged ventricular gaps (greater than 1-5 s), not associated with ectopic beats, were found in 26. No episodes of ventricular fibrillation were recorded. We conclude that many patients with vague symptoms suggestive of transient cerebral ischaemia or irregular heart action have significant and often dangerous dysrhythmias which can be diagnosed only by long-term recording of the ECG under fully ambulant conditions.
PMCID: PMC1675919  PMID: 1203673

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