Syncope is defined as a sudden transient loss of consciousness and postural tone due to cerebral hypoperfusion. Although no permanent medical sequelae should result from syncope itself, isolated or recurrent events are often dramatic and disrupt the lifestyle of affected individuals. Syncope is a common clinical problem that affects up to 3.5% of the general population.1 Strikingly, in close to 40% of cases, the exact cause of syncope remains elusive, and ≈30% of affected patients will experience recurrent episodes.1 

Neurally mediated syncope (NMS) is a common type of syncope (Figure 1⇓); clinical descriptions of it have been present in the medical literature for >100 years. Despite its prevalence, significant gaps in our understanding of its pathophysiology and treatment remain. The purpose of this review is to critically evaluate proposed theories that attempt to explain the pathophysiological mechanisms of NMS.



 Figure 1. 
Causes of syncope. NMS and orthostatic intolerance (OI) are the most frequent causes of unexplained syncope. Other causes may be hypoadrenergic (HypoAdr), cardiac (Card), neurological (Neurol), psychiatric (Psych), and/or idiopathic (Idiop).



The development of arterial vasodilation in the setting of relative or absolute bradycardia characterizes NMS. This syndrome has also been known as vasovagal reaction, neurocardiogenic syncope, emotional fainting, or reflex syncope. Related processes include situational fainting (ie, shaving syncope), hyperadrenergic and hypoadrenergic conditions, and hypotensive reactions resulting from drug administration.

We have classified NMS into several categories. These include central (for example, occurring in response to strong emotional stimulation), postural (associated with the upright position), and situational (after the specific stimulation of sensory or visceral afferents). Another classification considers the final hemodynamic characteristics of the patient and includes categories such as vasodepressor, bradycardic, or mixed NMS.2 One other classification relates to the clinical characteristics of the syncope and its response to treatment. This categorization includes malignant …

The Elusive Pathophysiology of Neurally Mediated Syncope

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.

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Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs.

Background —The wide range of clinical presentation of orthostatic vasovagal syncope suggests different underlying changes in the cardiac autonomic modulation.

Methods and Results —To evaluate the beat-by-beat modifications in the neural control of heart period preceding a syncopal event, we studied RR interval variability in 22 healthy subjects who experienced fainting for the first time during a 90° head-up tilt and in 22 control subjects by means of time-variant power spectral analysis. Sympathetic and vagal modulations to the sinoatrial node were assessed by the normalized power of the low-frequency (LF, ≈0.1-Hz) and high-frequency (HF, ≈0.25-Hz) oscillatory components of RR variability. When the patients were supine, no differences were observed in the hemodynamic and spectral parameters of the 2 groups. During the tilt procedure, RR, LFNU, and HFNU (NU=normalized units) values were relatively stable in control subjects. During early tilt (T1), subjects with syncope had reduced RR intervals compared with control subjects. In 13 subjects with syncope, RR decreased while LFNU and LF/HF increased in the last minute of tilt before syncope (T2). Conversely, in the remaining 9 fainters, LFNU and LF/HF decreased from T1 to T2 and HFNU increased slightly.

Conclusions —Two different patterns may be recognized in the cardiac autonomic changes preceding an occasional vasovagal event, namely, one characterized by a progressive increase of the marker of cardiac sympathetic modulation up to the onset of syncope, the other by a sympathetic inhibition with an impending vagal predominance. The recognition of different pathophysiological mechanisms in fainters may have important therapeutic implications.

Cardiac Autonomic Patterns Preceding Occasional Vasovagal Reactions in Healthy Humans

Falls are an important public health problem in older people. Medication use is considered a risk factor for falls. This study systematically reviewed recent studies to determine the medications that might be associated with the risk of falling in older people. We conducted a systematic review of prospective and retrospective studies identified through the MEDLINE and CINAHL databases that quantitatively assessed the contribution of medications to falls risk in participants ≥60 years old published in English between May 2008 and April 2013. The search identified 1,895 articles; 36 articles met the inclusion criteria. Of the 19 studies that investigated the effect of polypharmacy on the risk of falling, six studies reported that the risk of falling increased with polypharmacy. Data on the use of antihypertensive medications including calcium channel blockers, beta-blockers, and angiotensin system blocking medications were collected in 14 studies, with mixed results. Twenty-nine studies reported an association between the risk of falls and psychotropic medications including sedatives and hypnotics, antidepressants, and benzodiazepines. The use of sedatives and hypnotics and antidepressants including tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors appears to be related with an increased risk of falls. It is not clear if the use of antihypertensive medications is associated with the risk of falls in older people.

Medications associated with falls in older people: systematic review of publications from a recent 5-year period

Changes in heart rate, arterial pressure, norepinephrine and epinephrine levels were compared in 19 consecutive patients (10 men and 9 women, mean age 46 ± 16 years) with neurocardiogenic syncope and 11 age- and sex-matched control subjects (5 men and 6 women, mean age 49 ± 15 years) during head-up tilt testing. Norepinephrine and epinephrine levels were measured at the baseline supine position, in the initial upright position, every 90 seconds during the 70° upright tilt, at the time of termination due to hypotension and syncope (or at 15 minutes in control subjects), and at 40 seconds and 1 minute and 40 seconds in the supine position after terminating the headmp tilt test. Baseline norepinephrine, epinephrine and heart rate were slightly higher in patients. Despite a significant decrease in mean arterial pressure during head-up tilt testing in patients (51 ± 20 mm Hg, p It is concluded that diminished neuronal sympathetic activity and enhanced adrenomedullary activity is demonstrated during head-up tilt testing in patients with neurocardiogenic syncope.

Circulatory and catecholamine changes during head-up tilt testing in neurocardiogenic (vasovagal) syncope.

Transthoracic echocardiography and color flow Doppler have been shown to be of value in evaluating regurgitant St. Jude Medical (SJM) prostheses in the aortic valve position. 1 These studies have emphasized the limitations of this technique in diagnosing SJM mitral regurgitation because of flow masking and signal attenuation produced by the echo-reflective metallic valves. 2 Transesophageal echocardiography and color flow Doppler overcome these problems and show promise in evaluating normal functioning and regurgitant SJM mitral valves. 3,4 This report describes our transesophageal ultrasound experience with 28 normal functioning and 8 regurgitant SJM prostheses in the mitral valve position.

Transesophageal color flow doppler and echocardiographic features of normal and regurgitant st. jude medical prostheses in the aortic valve position

A frequent long-term complication of bioprosthetic valves is spontaneous degeneration of the cusps with clinical features of valve regurgitation or, less frequently, valve stenosis.1 Transthoracic echocardiography with cardiac Doppler is valuable in diagnosing stenosis of bioprosthetic valves.2 However, a major drawback of this approach is that all 3 bioprosthetic cusps are not consistently demonstrated owing to sound attenuation from the intervening chest wall and lungs, and to reverberation from the metal portion of the valve ring and stents. These problems are usually overcome by using a transesophageal ultrasound probe. We recently described our transesophageal echocardiographic investigations in predominantly regurgitant bioprosthetic valves.3 Those patients are not included in this study. To the best of our knowledge, there are no reports on stenotic bioprostheses studied by transesophageal echocardiography.

Mita Sheth

Papers

Circulatory and catecholamine changes during head-up tilt testing in neurocardiogenic (vasovagal) syncope.

Transesophageal color flow doppler and echocardiographic features of normal and regurgitant st. jude medical prostheses in the aortic valve position

Transesophageal echocardiographic features of stenotic bioprosthetic valves in the mitral and tricuspid valve positions.