Vasovagal Syncope: Hypothesis Focusing on Its Being a Clinical Feature Unique to Humans.

Humans live primarily in the upright position; as a result, there is a constant struggle between gravity and needed supply of blood flow to the brain. In certain circumstances brain blood supply may become temporarily insufficient, resulting in syncope. Among the numerous causes of syncope in humans, vasovagal syncope (VVS) is by far the most common. However, despite intensive research, many aspects of the pathophysiology of VVS remain unknown; among these, one of the least well understood is the basis for why VVS is restricted, among vertebrates, to Homo sapiens. In this manuscript we review proposals that have been offered in an attempt to address the issue of the origin of VVS and, although highly speculative, we suggest a new hypothesis (the "brain theory") to try to address the question of why humans, to the exclusion of other species, remain susceptible to VVS. This theory suggests that VVS evolved to offer protection to the brain's functional integrity under certain conditions of severe threat. Although seemingly a disadvantageous evolutionary adaptation, the faint causes the body to take on a gravitationally neutral position, and thereby provides a better chance of restoring brain blood supply and preserving long-term brain function.

Vasovagal syncope in humans and protective reactions in animals.

Vasovagal syncope (VVS) is not known to occur in animals, although other similar reflex responses are common. This review examines the possible relation of these latter presumably protective reflexes in animals to VVS in humans. The goal is to provide practitioners, and ultimately their patients, a meaningful understanding of the origins and appropriate management of this unpredictable affliction. This report utilized review of computer databases (e.g. PubMed) addressing VVS pathophysiology and origins, spontaneous transient loss of consciousness in animals, and comparative physiology. We also examined articles cited in the publications obtained by computer search and others suggested by colleagues. Articles were chosen based on those providing original observations and/or suggestions of novel mechanisms. In animals self-preservation is directed towards protection of the body through an escalation of behaviours depending on severity and proximity to danger. In humans self-preservation is directed not only to protection of the body, but also to protection of the brain's functional integrity. By virtue of loss of postural tone, the faint causes the body to assume a gravitationally neutral position, thereby offering a better chance of restoring brain blood supply and preserving brain function. Vasovagal syncope may seem to be a disadvantageous evolutionary adaptation. However, it is a reversible condition, that while exposing risk of injury and embarrassment, ultimately favours brain self-preservation in potentially threatening circumstances.

Syncope associated with documented paroxysmal atrioventricular block reproduced by adenosine 5' triphosphate injection.

AIMS: We sought to investigate in patients with syncope the relationship between documented paroxysmal atrioventricular block (AVB) of unknown mechanism and AVB induced by adenosine triphosphate (ATP) injection. METHODS AND RESULTS: We selected patients >45 years free of structural heart disease with syncope related to paroxysmal AVB documented by Holter or in-hospital monitoring, but without any trigger suggestive of vasovagal origin and with normal baseline electrocardiogram. Adenosine triphosphate test was performed according to the usual protocol. Nine patients (all females; mean age 66 ± 14.6 years; range: 48-81 years) matching the abovementioned criteria particularly documented spontaneous complete AVB with long ventricular pauses. Their mean QRS duration was 86.6 ± 14.1 ms and the mean PR interval was 161 ± 21.3 ms. In all patients, ATP induced a long ventricular pause related to AVB (mean duration 13.2 s; range from 7 to 56 s). After a mean follow-up duration of 42 ± 36 months, electrocardiogram (ECG) remained unchanged without progression to permanent AVB or appearance of intraventricular conduction disturbances. CONCLUSION: Some patients, predominantly older females, with 'normal' heart and ECG, have syncope associated with spontaneous AVB of unknown origin reproduced during the ATP test. They do not develop permanent AVB during follow-up. This unusual behaviour could be interpreted as an abnormal susceptibility to ATP and these patients could be considered to have 'ATP-sensitive AVB'. In this subgroup of syncope patients ATP test is useful.

Clinical laboratory testing: what is the role of tilt-table testing, active standing test, carotid massage, electrophysiological testing and ATP test in the syncope evaluation?

The first step in the diagnostic evaluation of patients with suspected syncope begins with an "initial evaluation" consisting of careful history taking, physical examination including orthostatic blood pressure measurement and electrocardiogram. However, even in expert centers the diagnostic yield of this "initial evaluation" is only approximately 50%. In the remaining cases in which a satisfactory diagnosis is either unknown or uncertain after initial assessment, additional clinical testing is needed. This article reviews the role of some of the more commonly used additional diagnostic tests, including: tilt-table testing, the active standing test, carotid sinus massage, electrophysiological testing, and the adenosine triphosphate (ATP) test. The role of angiography, exercise testing and imaging is noted briefly. Other clinical laboratory investigations, such as ambulatory ECG monitoring, are examined in other papers in this issue. In brief, clinical laboratory tests, carefully interpreted, may be useful in the evaluation of the basis of suspected syncope. However, these tests should be selected carefully and performed based on the pre-test probability inferred from the initial examination, and the less invasive tests should be used first.

Treatment of unexplained syncope: a multicenter, randomized trial of cardiac pacing guided by adenosine 5'-triphosphate testing.

BACKGROUND: The origin of 40% of syncope cases remains unknown even after a complete diagnostic workup. Previous studies have suggested that ATP testing has value in selecting successful therapy. This patient-blinded, multicenter, randomized superiority trial tested whether, in patients with syncope of unknown origin, selecting cardiac pacing in those with a positive ATP test leads to fewer recurrences than those who do not receive pacing. METHODS AND RESULTS: From 2000 to 2005, 80 consenting patients (mean age, 75.9±7.7 years; 81% women; 56% without diagnosed structural heart disease) with syncope of unknown origin and atrioventricular or sinoatrial block lasting >10 seconds (average, 17.9±6.8 seconds) under ATP administration (20-mg IV bolus) were recruited from 10 hospitals, implanted with programmable pacemakers, and randomized to either active pacing (dual-chamber pacing at 70 bpm) or backup pacing (atrial pacing at 30 bpm). Patients were followed up regularly for up to 5 years for any syncope recurrence, the primary outcome. Mean follow-up was 16 months. Syncope recurred in 8 of 39 patients (21%) randomized to active pacing and in 27 of 41 (66%) randomized to backup pacing (control), yielding a hazard ratio of 0.25 (95% confidence interval, 0.12-0.56). After recurrence, the 27 recurrent control patients were reprogrammed to active pacing, and only 1 reported subsequent syncope. CONCLUSION: This study suggests that, in elderly patients with syncope of unknown origin and positive ATP tests, active dual-chamber pacing reduces syncope recurrence risk by 75% (95% confidence interval, 44-88). CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com/ISRCTN00029383. Unique identifier: ISRCTN00029383.

Long-term follow-up of patients with short QT syndrome.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics and the long-term course of a large cohort of patients with short QT syndrome (SQTS). BACKGROUND: SQTS is a rare channelopathy characterized by an increased risk of sudden death. Data on the long-term outcome of SQTS patients are not available. METHODS: Fifty-three patients from the European Short QT Registry (75% males; median age: 26 years) were followed up for 64 ± 27 months. RESULTS: A familial or personal history of cardiac arrest was present in 89%. Sudden death was the clinical presentation in 32%. The average QTc was 314 ± 23 ms. A mutation in genes related to SQTS was found in 23% of the probands; most of them had a gain of function mutation in HERG (SQTS1). Twenty-four patients received an implantable cardioverter defibrillator, and 12 patients received long-term prophylaxis with hydroquinidine (HQ), which was effective in preventing the induction of ventricular arrhythmias. Patients with a HERG mutation had shorter QTc at baseline and a greater QTc prolongation after treatment with HQ. During follow-up, 2 already symptomatic patients received appropriate implantable cardioverter defibrillator shocks and 1 had syncope. Nonsustained polymorphic ventricular tachycardia was recorded in 3 patients. The event rate was 4.9% per year in the patients without antiarrhythmic therapy. No arrhythmic events occurred in patients receiving HQ. CONCLUSIONS: SQTS carries a high risk of sudden death in all age groups. Symptomatic patients have a high risk of recurrent arrhythmic events. HQ is effective in preventing ventricular tachyarrhythmia induction and arrhythmic events during long-term follow-up.

Assessment of carotid artery stenosis before coronary artery bypass surgery. Is it always necessary?

BACKGROUND: Extracranial internal carotid artery stenosis is a risk factor for perioperative stroke in patients undergoing coronary artery bypass surgery (CAB). Although selective and non-selective methods of preoperative carotid screening have been advocated, it remains unclear if this screening is clinically relevant. AIM: To test whether selective carotid screening is as effective as non-selective screening in detecting significant carotid disease. METHODS: The case records of patients consecutively undergoing CAB were reviewed. Patients were stratified retrospectively into high- or low-risk groups according to risk factors for significant carotid stenosis and perioperative stroke: peripheral vascular disease (PVD), carotid bruit, diabetes mellitus, age >70 years and/or history of cerebrovascular disease. Prevalence of carotid stenosis detected by ultrasonography, surgical management and perioperative stroke rates were determined in each group. RESULTS: Overall, 205 consecutive patients underwent preoperative carotid screening. The prevalence of significant carotid stenosis was 5.8%. Univariate analysis confirmed that PVD (P=0.005), carotid bruit (P=0.003) and diabetes mellitus (P=0.05) were significant risk factors for stenosis. Carotid stenosis was a risk factor for stroke (P=0.03). Prevalence of carotid stenosis was higher in the high-risk group (9.1%) than the low-risk group (1.2%) (P<0.05). All concomitant or staged carotid endarterectomies/CAB (5/205) and all patients who had perioperative strokes (5/205) were in the high-risk group (P=0.01). CONCLUSION: In our cohort, selective screening of patients aged >70 years, with carotid bruit, a history of cerebrovascular disease, diabetes mellitus or PVD would have reduced the screening load by 40%, with trivial impact on surgical management or neurological outcomes.

Atrial flutter after non-congenital cardiac surgery: incidence, predictors and outcome.

BACKGROUND: Atrial arrhythmias (AAs) occur frequently after cardiac surgery. However, most authors do not differentiate postoperative atrial fibrillation (AF) from atrial flutter (AFL). Our study sought to investigate the incidence and predictors of AFL following non-congenital cardiac surgery, and the long-term outcome of this arrhythmia. METHODS AND RESULTS: We conducted an observational, retrospective, single-centre study. Among 821 patients in sinus rhythm (SR) before non-congenital cardiac surgery, AFL occurred in 42 patients (5.1%) and AF in 77 (9.4%). Independent predictors of AAs were older age (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01-1.11, p = 0.02), low postoperative hemoglobin level (OR: 0.43, CI: 0.29-0.63, p < 0.0001) and long cross-clamp time (OR: 1.02, CI: 1.002-1.037, p = 0.03). Compared to AF patients, those with AFL were younger (67 ± 10 versus 72 ± 8 years, p = 0.005) and less likely to have valve surgery (57% versus 76%, p = 0.03). After conversion to SR, of 41/42 patients with AFL, 5 (12%) developed AFL and 5 (12%) had AF within a mean follow-up of 9.6 ± 8.4 months: only 32% of patients were on long-term antiarrhythmic therapy and 5% had radiofrequency ablation of AFL in the early postoperative period. CONCLUSION: AFL following non-congenital cardiac surgery is not frequent. Compared to patients in AF, those with AFL are younger and less likely to have valve surgery. After conversion of AFL to SR, recurrence rate of AAs is relatively low. Therefore, AFL occurring in this setting does not require systematic catheter ablation in the postoperative period.

Cardiac multislice spiral computed tomography as an alternative to coronary angiography in the preoperative assessment of coronary artery disease before aortic valve surgery: a management outcome study.

BACKGROUND: Conventional coronary angiography (CA) is still recommended before valvular surgery. Preliminary studies suggest that multislice spiral computed tomography coronary angiography (MSCT-CA) can be used to rule out coronary artery disease (CAD). AIM: To assess prospectively the safety of ruling out CAD before surgery solely on the basis of normal MSCT-CA in patients with severe aortic valve disease. METHODS: We included all consecutive patients scheduled for aortic valve surgery. We first estimated the calcium score (Agatston score equivalent [ASE]). Patients underwent injected MSCT if the ASE was<1000. CA was cancelled when MSCT-CA quality was sufficient and showed no significant CAD. Our primary endpoint was the occurrence of perioperative myocardial infarction in patients who underwent surgery with no prior CA. RESULTS: Between 1st July 2005 and 30th June 2008, we included 199 patients with severe aortic valve disease: 118 men (59%); mean age 69+/-12 years; 63 patients (32%) underwent CA directly because the ASE was > or =1000. Of 136 patients who underwent MSCT-CA, 106 (78%) had a normal MSCT-CA and underwent aortic valve surgery without prior CA; CA was performed in 30 patients because of abnormal (n=18) or bad quality (n=12) MSCT-CA. One patient of the 106 (0.94%, 95% confidence interval 0.17-5.15) had a perioperative myocardial infarction. CONCLUSIONS: When the ASE is <1000, MSCT is safe and may be recommended instead of CA as a first-line means of ruling out CAD in patients with severe aortic valve disease.

Cardiac tamponade in medical patients: a 10-year follow-up survey.

OBJECTIVES: Cardiac tamponade represents a life-threatening condition that may complicate almost any cause of pericarditis. We conducted a 10-year prospective survey on patients with cardiac tamponade requiring an emergency drainage. METHODS: From 1996 to 2005, 114 consecutive patients were admitted to the University Hospital of Brest for medical cardiac tamponade. Data on medical history, and volume, characteristics and histology of the pericardial fluid as well as short- and long-term follow-up data were collected. RESULTS: Malignant disease was the primary cause of medical tamponade (74 patients; 65%), followed by viral history (11; 10%) and intra-pericardial bleeding due to anti-coagulation treatment (4; 3%). In 12 cases, aetiology remained unknown (10%). Pericardiocentesis was immediately performed in 80 cases and surgical pericardiotomy in 34. The mean volume drained was 593 +/- 313 ml. In-hospital mortality was 10% without any difference between malignant and non-malignant diseases (p = 0.8). One-year mortality was 76.5% in patients with malignant disease and 13.3% in those without malignant disease (p < 0.0001). Median survival in case of malignant disease was 150 days. CONCLUSION: Compared to previously published data, our survey shows a decrease in some historical causes of tamponade such as tuberculosis, myxoedema or uraemia. The leading cause is currently malignant disease, which carries a very poor prognosis.

Accuracy of multislice computed tomography in the preoperative assessment of coronary disease in patients with aortic valve stenosis.

OBJECTIVES: To evaluate multislice computed tomography (MSCT) as an alternative to coronary angiography, we prospectively studied its diagnostic accuracy for the detection of significant coronary artery lesions in patients with significant aortic valve stenosis undergoing valve surgery. BACKGROUND: In patients with aortic valve stenosis, coronary angiography is still recommended before surgery. Multislice computed tomography is a promising noninvasive technique for the detection of significant coronary artery lesions. METHODS: Fifty-five consecutive patients scheduled for coronary angiography in the preoperative assessment of aortic valve stenosis underwent 16-slice MSCT 24 h before coronary angiography. We analyzed coronary lesions, image quality, and arterial calcium score. RESULTS: The sensitivity of the MSCT-based strategy in detecting significant stenosis was 100%, and its specificity 80%. The positive and negative predictive values were respectively 55% and 100%. For calcium scores <1,000 (77% of patients), MSCT detected all patients without coronary artery disease, enabling conventional coronary angiography to be avoided in 35 of 55 cases (80%). For calcium scores >1,000, MSCT enabled conventional coronary angiography to be avoided in only 6% of cases, either because significant stenosis was found with a possible indication of revascularization, or because the examination was not interpretable. CONCLUSIONS: The results of this initial experience in relatively few patients suggest that MSCT-based coronary angiography may serve as an alternative to invasive coronary angiography to rule out significant coronary artery disease in patients scheduled for elective aortic valve replacement. Larger studies are necessary to fully explore the potential of coronary MSCT to improve preoperative risk stratification.

Epidemiology, clinical features, and follow-up of patients with syncope and a positive adenosine triphosphate test result.

OBJECTIVES: We sought to evaluate epidemiology, clinical features, and outcomes of patients with syncope and an abnormal response to adenosine triphosphate (ATP). BACKGROUND: Syncope remains of unknown origin in almost 30% of the patients. Injection of ATP induces in some of these patients, but not in control patients, a ventricular pause > or =6 s. METHODS: Patients with syncope of unknown origin had an intravenous injection of 20 mg of ATP. All patients had a tilt test. RESULTS: Among 214 patients, 19 (8.9%) had a positive ATP test result. The proportion of positive test results was higher (p < 0.002) in women (14.3%) than in men (2.2%). Ten patients (4.7%) had positive ATP and tilt test results. These patients (exclusively women) were older (p < 0.05) at the time of their fist syncope than the 67 patients with a negative ATP test result but a positive tilt test result. There was a trend for these two test results to be correlated (p = 0.07). Side effects were of short duration and benign. The mean duration of pauses was longer in women (p = 0.009). During a mean period of 31 +/- 14 months, recurrences of syncope were reported in 25% of patients. CONCLUSIONS: The ATP test is a safe test with an "abnormal" result in <10% of patients with syncope of unknown origin. The profile of these patients is characteristic.