2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope

In the paper

“However, the devices have been shown to improve care in only the subset of patients who are older, have asystole documented on the ILR, and whose tilt test results were negative, probably because many of the diagnoses are of vasovagal syncope.”

What the sources say

• ?Not checked — no full text of the sourcecites [105] Krahn, 1995, The etiology of syncope in patients with negative tilt table and electrophysiological testing, Circulation source
• Disputed

  The Abstract (page not provided) concludes that prolonged monitoring was effective and safe in patients with problematic syncope, not only in the specified subset. The Symptom-Rhythm Correlation section (page not provided) reports diagnoses leading to pacemakers and treatment for tachyarrhythmias, but does not establish an older, recorder-documented-asystole, negative-tilt subgroup as the only patients whose care improved. It reports seven clinical diagnoses of neurally mediated syncope, not that many diagnoses were vasovagal. (LLM, conf=0.86)

  Checked by a reasoning model — may be wrong.

  cites [106] Krahn, 1999, Use of an extended monitoring strategy in patients with problematic syncope. Reveal Investigators, Circulation sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract reports ILR-documented asystole in both tilt-negative and tilt-positive patients, and Clinical Implications reports ILR-guided therapy in 16 patients. But the paper does not show that care improves only for older, tilt-negative patients; Clinical Implications explicitly says the efficacy of therapy in preventing further syncope remains to be proved. The Discussion also reports asystolic syncope in tilt-positive patients. (LLM, conf=0.88)

  cites [107] Moya, 2001, International Study on Syncope of Uncertain Etiology (ISSUE) Investigators. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope, Circulation sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [108] Moya, 2008, Reproducibility of electrocardiographic findings in patients with suspected reflex neurally-mediated syncope, Am J Cardiol source
• ?Not checked — no full text of the sourcecites [109] Solano, 2004, Incidence, diagnostic yield and safety of the implantable loop-recorder to detect the mechanism of syncope in patients with and without structural heart disease, Eur Heart J source
• ?Not checked — no full text of the sourcecites [110] Brignole, 2006, International Study on Syncope of Uncertain Etiology (ISSUE) 2 Group. Early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected neurally mediated syncope, Eur Heart J source
• ?Not checked — no full text of the sourcecites [111] Brignole, 2012, Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial, Circulation source
• Partly supported

  The Conclusions (page unavailable) report that cardiac pacing was very effective in patients with ILR-documented asystole and a negative tilt test. The claim instead assigns that benefit to the implantable loop recorder, which the Study protocol (page unavailable) used to document events before pacemaker treatment. The Conclusions say evidence for pacing in tilt-positive patients was insufficient, not that benefit is possible only in the tilt-negative group; they do not give vasovagal diagnoses as the reason for the difference. (LLM, conf=0.88)

  cites [112] Brignole, 2014, Benefit of pacemaker therapy in patients with presumed neurally mediated syncope and documented asystole is greater when tilt test is negative: an analysis from the third International Study on Syncope of Uncertain Etiology (ISSUE-3), Circ Arrhythm Electrophysiol sourceExperimental — accuracy not yet measured

In the paper

“and more than 75% are female.7–9,11–14,16”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source
• ?Not checked — no full text of the sourcecites [8] Schondorf, 1993, Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?, Neurology source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [9] Low, 1995, Postural tachycardia syndrome (POTS), Neurology
• Supported

  The paper’s introductory passage (labeled Abstract in our copy) says females predominate in POTS and orthostatic intolerance at a ratio of about 5:1. That corresponds to approximately 83% female, supporting the claim that more than 75% of POTS patients are female. (LLM, conf=0.90)

  cites [11] Singer, 2012, Postural tachycardia in children and adolescents: what is abnormal?, J Pediatr source
• ?Not checked — no full text of the sourcecites [12] Garland, 2007, The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome, Neurology source
• Supported

  The Clinical Features section reports a consistent female-to-male ratio of 5:1 among patients evaluated, equivalent to about 83% female. The Abstract Results also states that females predominate by 5:1, supporting the claim that more than 75% are female. (LLM, conf=0.95)

  cites [13] Low, 2009, Postural tachycardia syndrome (POTS), J Cardiovasc Electrophysiol source
• ?Not checked — no full text of the sourcecites [14] Robertson, 1999, The epidemic of orthostatic tachycardia and orthostatic intolerance, Am J Med Sci source
• ?Not checked — no full text of the sourcecites [16] Freeman, 2011, Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome, Clin Auton Res source

In the paper

“This abrupt reduction in venous return decreases cardiac output and blood pressure, which are rapidly sensed by the arterial and cardiopulmonary baroreceptors, thus triggering sympathetic noradrenergic vasoconstriction and venoconstriction accompanied by an increase in heart rate.73”

What the sources say

• Partly supported

  The Pathophysiology section (page unavailable) says that standing reduces venous return, cardiac output, and blood pressure, and that arterial and cardiopulmonary baroreceptors detect these changes. The Ventricular Theory section describes a reflex increase in sympathetic activity, peripheral resistance, and heart rate when blood pressure falls. Our copy does not specify venoconstriction as part of that response or characterize the vasoconstriction as noradrenergic. (LLM, conf=0.85)

  cites [73] Mosqueda-Garcia, 2000, The elusive pathophysiology of neurally mediated syncope, Circulation sourceExperimental — accuracy not yet measured

In the paper

“A number of mechanisms have been described in patients with POTS,18 including autonomic denervation, hypovolemia, hyperadrenergic stimulation, deconditioning, and hypervigilance”

What the sources say

• Supported

  The Classic Pathophysiology and POTS Subtypes section describes peripheral sympathetic denervation. The Figure lists hypovolemia, deconditioning, and a hyperadrenergic state among POTS mechanisms, while the table in Conclusions and Perspective includes somatic hypervigilance. No page numbers are supplied in our copy. (LLM, conf=0.92)

  cites [18] Benarroch, 2012, Postural tachycardia syndrome: a heterogeneous and multifactorial disorder, Mayo Clin Proc source

In the paper

“low-dose propranolol (10–20 mg PO) acutely lowers standing heart rate and improves symptoms in patients with POTS, while higher doses of propranolol are less well tolerated.42”

What the sources say

• Partly supported

  The Abstract’s Methods and Results report that oral propranolol 20 mg acutely lowered standing heart rate and improved symptoms in patients with POTS; symptom improvement was smaller with 80 mg. The Discussion’s Clinical Significance section says patients commonly receive and generally tolerate 10–20 mg, but the acute trial tested 20 mg, not 10 mg. The paper suggests higher doses may worsen symptoms rather than establishing that they are generally less well tolerated. (LLM, conf=0.86)

  cites [42] Raj, 2009, Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more, Circulation sourceExperimental — accuracy not yet measured

In the paper

“Ivabradine eliminated symptoms in 70% of patients and increased exercise performance.”

What the sources say

• Partly supported

  The Discussion and Conclusions (pp. 1327–1329) say ivabradine eliminated more than 70% of baseline symptoms, not all symptoms in 70% of patients. The Results (p. 1325) report complete symptom elimination in 9 of 21 patients, while exercise duration and capacity increased with ivabradine. Thus the exercise-performance finding is supported, but the claim confuses the percentage of symptoms eliminated with the percentage of patients whose symptoms were eliminated. (LLM, conf=0.92)

  cites [63] Cappato, 2012, Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation, J oAm Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“Treadmill exercise testing might be useful to document an exaggerated tachycardic response to exertion,59 although this assertion has not been validated.”

What the sources say

• Supported

  The Results report that exercise testing documented a markedly enhanced heart-rate response to low-grade exercise in four patients, supporting the cited suggestion that treadmill testing might help document such a response. The sentence’s qualification that this use has not been validated is consistent with the paper’s limited exercise-test observations. (LLM, conf=0.90)

  cites [59] Morillo, 1994, Mechanism of ”inappropriate” sinus tachycardia. Role of sympathovagal balance, Circulation source

In the paper

“The drug blunts orthostatic tachycardia and can improve chronic symptoms but is limited by adverse effects such as diarrhea, abdominal pain and cramps, nausea, and increased urinary urgency and frequency.45,46”

What the sources say

• Partly supported

  The Pyridostigmine Hemodynamics and Symptoms sections report reduced standing heart rate and improved symptom burden over four hours. Study Limitations says long-term efficacy and tolerability are unknown and identifies only increased gastrointestinal motility as a possible limiting side effect; it does not document sustained symptom improvement or the listed adverse effects. (LLM, conf=0.90)

  cites [45] Raj, 2005, Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome, Circulation sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [46] Kanjwal, 2011, Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience, Pacing Clin Electrophysiol source

In the paper

“Deconditioned patients with POTS have reduced left ventricular mass, stroke volume, and blood volume,35 which improve with exercise training.”

What the sources say

• Partly supported

  The Discussion reports that patients with POTS had lower left ventricular mass and blood volume than sedentary controls, as well as smaller upright stroke volume. The Results report that exercise training increased left ventricular mass and blood volume, but do not establish that stroke volume also improved after training. (LLM, conf=0.84)

  cites [35] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“For many years, vasovagal syncope was thought to be the result of loss of peripheral sympathetic activity, and the proposed pathophysiologic mechanism leading to vasovagal syncope was the blunting or cessation of MSNA.82–84”

What the sources say

• ?Not checked — no full text of the sourcecites [82] Morillo, 1997, Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope, Circulation source
• Supported

  The Introduction (page not supplied) describes sympathetic withdrawal as a proposed explanation for vasodilation in neurally mediated syncope. It also reports an earlier observation in which muscle sympathetic nerve activity disappeared before a hypotensive attack, supporting the citing sentence’s description of the historical proposed mechanism. (LLM, conf=0.91)

  cites [83] Mosqueda-Garcia, 1997, Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt, J Clin Invest source
• ?Not checked — no full text of the sourcecites [84] Jardine, 2002, Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope, Am J Physiol Heart Circ Physiol source

In the paper

“The initial reduction in blood pressure during vasovagal syncope provoked by orthostatic stress is driven by a 50% decline in cardiac output, with coincident vasodilatation in only a subset of patients.78–80”

What the sources say

• ?Not checked — no full text of the sourcecites [78] Verheyden, 2008, Steep fall in cardiac output is main determinant of hypotension during drug-free and nitroglycerine-induced orthostatic vasovagal syncope, Heart Rhythm source
• ?Not checked — no full text of the sourcecites [79] Gisolf, 2004, Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response, J Am Coll Cardiol source
• Partly supported

  The Vasovagal episode section reports a marked fall in cardiac output in all patients before tilt-back, and The final vasovagal response section describes the nitroglycerine-triggered response as cardiac-output-mediated. Our copy does not quantify that fall as roughly 50% or report coincident vasodilation in a subset; it says systemic vascular resistance did not fall before the response. The findings also concern nitroglycerine-provoked tilt testing, rather than orthostatic vasovagal syncope generally (page numbers unavailable). (LLM, conf=0.88)

  cites [80] Verheyden, 2007, Impact of age on the vasovagal response provoked by sublingual nitroglycerine in routine tilt testing, Clin Sci sourceExperimental — accuracy not yet measured

In the paper

“Nonetheless, the scores serve as useful reminders of important diagnostic points, and they form reproducible criteria for entry into observational, genetic, and randomized, controlled interventional trials.91,96,97”

What the sources say

• ?Not checked — no full text of the sourcecites [91] Sheldon, 2006, Diagnostic criteria for vasovagal syncope based on a quantitative history, Eur Heart J source
• Partly supported

  The Methods describe predefined diagnostic criteria for syncope and strict adherence to them, including criteria for typical vasovagal syncope. The paper does not say that diagnostic scores serve as reminders or that scores provide entry criteria for observational, genetic, or randomized trials. (LLM, conf=0.76)

  cites [96] Alboni, 2001, Diagnostic value of history in patients with syncope with or without heart disease, J Am Coll Cardiol sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [97] Sud, 2009, Predicting the cause of syncope from clinical history in patients undergoing prolonged monitoring, Heart Rhythm source

In the paper

“Sympathetic vaso-constriction and baroreflex sensitivity prior to the onset of presyncope were well preserved, and muscle sympathetic nerve activity (MSNA) withdrawal occurred late after the onset of hypotension.”

What the sources say

• Partly supported

  The section “Role of sympathetic activity and total peripheral resistance in syncope” says sympathetic withdrawal occurs at presyncope, well after the initial blood-pressure decrease. It does not establish that baroreflex sensitivity was preserved, and it reports that total peripheral resistance fell before the obvious MSNA reduction in most presyncopal individuals, rather than establishing preserved vasoconstriction generally. No page number is available in our copy. (LLM, conf=0.86)

  cites [81] Fu, 2014, Pathophysiology of neurally mediated syncope: Role of cardiac output and total peripheral resistance, Auton Neurosci sourceExperimental — accuracy not yet measured

In the paper

“MSNA was normal in the normal blood pressure phenotype and increased in the low blood pressure phenotype group.”

What the sources say

• Supported

  The Abstract reports that the sympathetic nerve-firing response during head-up tilt was normal in the normal-blood-pressure phenotype and accentuated in the low-blood-pressure phenotype. The discussion likewise says MSNA increased normally in the former group and at twice the normal rate in the latter; the finding concerns the response to tilt. (LLM, conf=0.90)

  cites [87] Vaddadi, 2011, Recurrent postural vasovagal syncope: sympathetic nervous system phenotypes, Circ Arrhythm Electrophysiol source

In the paper

“Both phenotypes have reduced NE availability, which ultimately impairs the neurocirculatory response to orthostatic stress.87”

What the sources say

• Supported

  The Conclusions state that both recurrent vasovagal syncope phenotypes have lowered norepinephrine availability, impairing the neural circulatory response. The Cellular: SNPs section also reports a failure of the normal response to orthostatic stress in both phenotypes. (LLM, conf=0.95)

  cites [87] Vaddadi, 2011, Recurrent postural vasovagal syncope: sympathetic nervous system phenotypes, Circ Arrhythm Electrophysiol source

In the paper

“Fu and Levine81 reported a moderate decline in cardiac output with coincident vasodilation in the majority of participants with presyncope and no changes in total peripheral resistance during presyncope in a minority of participants.”

What the sources say

• Supported

  The Introduction reports a moderate fall in cardiac output with coincident vasodilatation in 64% of presyncopal individuals. It reports no change in total peripheral resistance at presyncope in the smaller 36% subset, whose cardiac-output fall was severe and predominantly driven by reduced heart rate. (LLM, conf=0.95)

  cites [81] Fu, 2014, Pathophysiology of neurally mediated syncope: Role of cardiac output and total peripheral resistance, Auton Neurosci source

In the paper

“In some patients, however, decreased preload does not play a dominant role in causing symptoms; instead, peripheral vasodilation plays an important role.”

What the sources say

• Partly supported

  The Introduction reports that most presyncopal individuals had a moderate fall in cardiac output with coincident vasodilation, supporting an important role for vasodilation in some cases. The Contribution of cardiac output to syncope section also links reduced venous return to falling stroke volume; it does not establish that decreased preload is not the dominant cause of symptoms in those individuals. Page numbers are unavailable in our copy. (LLM, conf=0.82)

  cites [81] Fu, 2014, Pathophysiology of neurally mediated syncope: Role of cardiac output and total peripheral resistance, Auton Neurosci sourceExperimental — accuracy not yet measured

In the paper

“Based on this evidence, there have been several observational studies and 3 small, randomized trials on serotonin transport inhibitors for the prevention of vasovagal syncope.130–132”

What the sources say

• Supported

  This paper is one of the small randomized trials identified by the grouped citations. Its Study population section reports 96 patients randomized among fluoxetine, propranolol, and placebo, and its Discussion describes it as a prospective, placebo-controlled study of treatment for vasovagal syncope. The citation identifies a trial; it need not independently establish the total of three trials. (LLM, conf=0.92)

  cites [130] Theodorakis, 2006, Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study, Europace source
• Partly supported

  The Subjects’ Characteristics and Lower Body Negative Pressure sections describe a small randomized Paxil-versus-placebo trial. But the Present Study section says it tested provoked presyncope in healthy volunteers, not prevention of vasovagal syncope in patients; it also says the effect in patients with a history of syncope remains unknown. As one of three citations, this paper establishes the existence of this trial, not the total count. (LLM, conf=0.84)

  cites [131] Takata, 2002, Serotonin reuptake inhibitor (Paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers, Circulation sourceExperimental — accuracy not yet measured
• Supported

  The Study protocol describes a small randomized, blinded trial of paroxetine versus placebo in 68 patients, making this paper one of the trials the citation identifies. The Discussion also describes earlier serotonin-reuptake-inhibitor studies that were not placebo-controlled. This paper does not itself establish the total of three randomized trials, but the citation identifies it as one of them. (LLM, conf=0.91)

  cites [132] Di Girolamo, 1999, Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study, J Am Coll Cardiol source

In the paper

“Although earlier observational, open-label, and single-blind studies have been uniformly positive, the results of 2 subsequent double-blind studies in adults were negative.133–138”

What the sources say

• ?Not checked — no full text of the sourcecites [133] Connolly, 1999, The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope, J Am Coll Cardiol source
• Partly supported

  The Comparison With the North American Vasovagal Pacemaker Study section says this study and an earlier randomized study found favorable results, and that neither was blinded. The Study Limitations section also confirms that this trial was unblinded. Our copy does not establish that observational and single-blind studies were uniformly positive or report the two subsequent negative double-blind studies. Page numbers were not available in the indexed passages. (LLM, conf=0.88)

  cites [134] Sutton, 2000, Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope: pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators, Circulation sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not provided) reports a favorable pacing result and describes earlier studies as suggesting benefit. The Study Limitations (page not provided) state that this trial was not blinded. Our copy does not report two subsequent negative double-blind studies, so it supports only the earlier-positive part of the sentence. (LLM, conf=0.86)

  cites [135] Ammirati, 2001, Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial, Circulation sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [136] Connolly, 2003, Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial, JAMA source
• Partly supported

  The Comparison with previous studies section reports positive results for dual-chamber observational studies and three randomized open studies, and says that VPS II and SYNPACE did not confirm pacing efficacy. It also says observational studies found single-chamber VVI pacing ineffective, so the earlier studies were not uniformly positive; the passage does not establish the claim about single-blind studies. No page number is available in our copy. (LLM, conf=0.88)

  cites [137] Raviele, 2004, Vasovagal Syncope and Pacing Trial Investigators. A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE), Eur Heart J sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page unavailable) says two randomized controlled trials failed to show that pacing was superior to sham pacing in patients with positive tilt tests, supporting the negative-trial portion. It mentions earlier pacing studies but does not say that the observational, open-label, and single-blind studies were uniformly positive. (LLM, conf=0.86)

  cites [138] Sud, 2007, Implications of mechanism of bradycardia on response to pacing in patients with unexplained syncope, Europace sourceExperimental — accuracy not yet measured

In the paper

“However, syncope recurred in a substantial minority of patients, and the study was open label.”

What the sources say

• Partly supported

  The Population section reports syncope recurrence in 31 of 98 patients (31.6%) in the maneuver group and 56 of 110 (50.9%) in the conventional-treatment group, supporting ‘a substantial minority.’ The Study limitations section says patients were blinded to the randomization outcome, while physicians were not; describing the study without qualification as open label overlooks that patient blinding. (LLM, conf=0.88)

  cites [120] van Dijk, 2006, PC-Trial Investigators. Effectiveness of physical counter pressure maneuvers in preventing vasovagal syncope: the Physical Counter pressure Manoeuvres Trial (PC-Trial), J Am Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“While results have generally been positive in uncontrolled trials and short-term controlled trials, those of long-term, placebo-controlled prospective trials have been less encouraging.”

What the sources say

• ?Not checked — no full text of the sourcecites [113] Sutton, 2012, Key challenges in the current management of syncope, Nat Rev Cardiol source
• ?Not checked — no full text of the sourcecites [114] Kuriachan, 2008, Evidence-based treatment for vasovagal syncope, Heart Rhythm source
• ?Not checked — no full text of the sourcecites [115] Vyas, 2013, Are treatments for vasovagal syncope effective? A meta-analysis, Int J Cardiol source
• ?Could not verify

  The Findings and Discussion compare diagnostic management in hospitals with and without syncope units; the Conclusions discuss the need for further studies of those units. Searches for long-term placebo-controlled trials and for lifestyle or medical therapies found no passage comparing treatment-trial outcomes. (LLM, conf=0.77)

  cites [116] Brignole, 2003, Management of syncope referred urgently to general hospitals with and without syncope units, Europace sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [117] Sutton, 2013, Treatment of reflex syncope, J Med Diagn Meth source

In the paper

“Typically, the vasovagal reflex is both hypotensive and cardioinhibitory, and there is emerging evidence that tilt-table testing identifies patients with predominant reflex hypotension.112”

What the sources say

• Supported

  The Discussion (page unavailable) says hypotension plays a major role in tilt-induced neurally mediated syncope and usually precedes bradycardia, including in cardioinhibitory cases. It also infers from the study’s findings that a vasodepressive mechanism dominates in tilt-positive patients, supporting the claim’s qualified description of emerging evidence. (LLM, conf=0.89)

  cites [112] Brignole, 2014, Benefit of pacemaker therapy in patients with presumed neurally mediated syncope and documented asystole is greater when tilt test is negative: an analysis from the third International Study on Syncope of Uncertain Etiology (ISSUE-3), Circ Arrhythm Electrophysiol source

In the paper

“A recent subanalysis of ISSUE-3 showed that the syncope recurrence rate for patients with asystole, with or without syncope, was 5% for patients with negative tilt test results and 55% for those with positive tilt test results, which is similar to the results observed in controls without pacing.112”

What the sources say

• Partly supported

  The Results report 21-month syncope recurrence estimates of 5% after a negative tilt test and 55% after a positive tilt test among patients with ILR-documented asystole who received pacemakers. They also say the positive-tilt rate was similar to that in untreated controls. The passages do not establish the claim’s additional qualifier that the documented asystole occurred “with or without syncope.” (LLM, conf=0.82)

  cites [112] Brignole, 2014, Benefit of pacemaker therapy in patients with presumed neurally mediated syncope and documented asystole is greater when tilt test is negative: an analysis from the third International Study on Syncope of Uncertain Etiology (ISSUE-3), Circ Arrhythm Electrophysiol sourceExperimental — accuracy not yet measured

In the paper

“The 10-minute standing tests for POTS provided reasonable accuracy in a small study on adults, but these tests have not been validated for pediatric populations.143”

What the sources say

• Supported

  The Results report 87% sensitivity and 67% specificity for the 10-minute stand test, and the Discussion calls it the most accurate test. The Methods describe a small sample of adults, while the Discussion says the findings cannot be extrapolated to children because all subjects were over 18. Page numbers were not supplied. (LLM, conf=0.92)

  cites [143] Plash, 2013, Diagnosing postural tachycardia syndrome: comparison of tilt testing compared with standing haemodynamics, Clin Sci source

In the paper

“The diagnostic standard for tilt-table testing for POTS in young people requires symptoms of orthostatic intolerance and an orthostatic increase in heart rate of at least 40 bpm, which is greater than in adults.11”

What the sources say

• Partly supported

  The Discussion’s “Pediatric OI” criteria require orthostatic symptoms and a heart-rate increase of at least 40 bpm within five minutes of head-up tilt; the Discussion also identifies the adult threshold as 30 bpm. But its “Pediatric POTS” criteria additionally require an absolute orthostatic heart rate of at least 130 bpm for ages 13 and younger or 120 bpm for ages 14 and older. The citing sentence omits that additional POTS requirement. Page numbers were not provided in our copy. (LLM, conf=0.89)

  cites [11] Singer, 2012, Postural tachycardia in children and adolescents: what is abnormal?, J Pediatr sourceExperimental — accuracy not yet measured

In the paper

“These patients were refractory to multiple medications and appeared to benefit from cardiac pacing.”

What the sources say

• Partly supported

  The Recorded Events section reports fewer syncopal episodes during pacing, supporting the apparent benefit. The Conclusions recommend pacing when medical treatment has failed or been declined, but the paper does not establish that these patients were refractory to multiple medications. (LLM, conf=0.86)

  cites [142] McLeod, 1999, Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures, Heart sourceExperimental — accuracy not yet measured

In the paper

“Most patients present with POTS between the ages of 15 and 25 years,7”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source

In the paper

“The final minimum consensus was 76% and the mean was 94%.”

In the paper

“As much as possible, we made recommendations based on published evidence.”

In the paper

“The symptoms associated with POTS are those that occur with standing, such as lightheadedness and palpitations; not associated with particular postures, such as bloating, nausea, diarrhea, and abdominal pain; and systemic, such as fatigue, sleep disturbance, and migraine headaches.7”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc source

In the paper

“The recommendations and definitions in this document are based on the consensus of the full writing group following the Heart Rhythm Society’s process for establishing consensus-based guidance for clinical care.”

In the paper

“The prevalence of POTS is approximately 0.2%, with little variance among 4 published reports.9,12,14,15”

What the sources say

• Not checked yetcites [9] Low, 1995, Postural tachycardia syndrome (POTS), Neurology
• ?Not checked — no full text of the sourcecites [12] Garland, 2007, The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome, Neurology source
• ?Not checked — no full text of the sourcecites [14] Robertson, 1999, The epidemic of orthostatic tachycardia and orthostatic intolerance, Am J Med Sci source
• ?Not checked — no full text of the sourcecites [15] Schondorf, 1999, Orthostatic intolerance in the chronic fatigue syndrome, J Auton Nerv Syst source

In the paper

“All members of the writing group and peer reviewers provided disclosure statements of all relationships that might present real or perceived conflicts of interest, as shown in the Appendices.”

In the paper

“POTS is a systemic illness, with postural tachycardia one of several criteria.”

In the paper

“To identify consensus, we conducted surveys of the entire writing group, using a predefined threshold for agreement as a vote of >75% on each recommendation.”

In the paper

“Patients with POTS and patients with IST can present similar symptoms, but IST is induced by both physiologic and emotional stresses, while POTS is generally induced only by orthostatic stress.”

In the paper

“The median age of the first syncope is approximately 14 years, and most people with vasovagal syncope will have had their first syncope before age 40.67”

What the sources say

• ?Not checked — no full text of the sourcecites [67] Sheldon, 2006, Investigators of the Syncope Symptom Study and the Prevention of Syncope Trial. Age of first faint in patients with vasovagal syncope, J Cardiovasc Electrophysiol source

In the paper

“The estimate for emergency departments is obscured by the fact that approximately 35% of patients with syncope remain undiagnosed.”

In the paper

“a tilt-table test might be helpful because it can provide vital signs over more prolonged periods than a simple stand test.”

In the paper

“In general, primary success rates are reasonably good, but there is a high rate of symptom recurrence, and the complication rates are significant.”

In the paper

“The treatment of POTS is difficult; there are no therapies that are uniformly successful, and combinations of approaches are often needed.”

In the paper

“The overall 1-year recurrence rate in many reports is approximately 25%–35%, and this rate can be predicted by the number of syncopes in the year prior to assessment.68”

What the sources say

• ?Not checked — no full text of the sourcecites [68] Sumner, 2010, Prevention of Syncope Trial I. Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden, J Cardiovasc Electrophysiol source

In the paper

“These patients are hypersensitive to isoproterenol and have marked tachycardic responses to dosages that do not induce hemodynamic changes in healthy individuals.33”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Abe, 2000, Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome, J Cardiovasc Pharmacol source

In the paper

“Radiofrequency sinus node modification for the sinus tachycardia of POTS is not recommended, because it often worsens symptoms and occasionally results in the patient requiring a pacemaker.50”

What the sources say

• ?Not checked — no full text of the sourcecites [50] Shen, 2001, Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?, Pacing Clin Electrophysiol source

In the paper

“Expert centers report anecdotally that 1 L of normal saline infused over 1 hour decreases orthostatic tachycardia and improves symptoms for several hours to 2 days.40,41”

What the sources say

• ?Not checked — no full text of the sourcecites [40] Jacob, 1997, Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia, Circulation source
• ?Not checked — no full text of the sourcecites [41] Gordon, 2000, Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome, Clin Auton Res source

In the paper

“Approximately 30%–50% of patients with syncope, however, are diagnosed with an autonomically mediated form of syncope, and most of these are vasovagal.”

In the paper

“These complications include requirements for permanent pacing, transient or permanent phrenic nerve paralysis, and transient superior vena cava syndrome.”

In the paper

“This manifestation, which occurs in up to 50% of patients, is associated with systolic blood pressure increases of ≥10 mm Hg while standing upright for 10 minutes and plasma norepinephrine levels ≥600 pg/mL while standing.”

In the paper

“Detailed physiologic and psychometric studies showed that although anxiety is commonly present in POTS, the heart rate response to orthostatic stress is not caused by anxiety but is instead a response to an underlying physiologic abnormality.”

What the sources say

• ?Not checked — no full text of the sourcecites [36] Masuki, 2007, Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety, J Appl Physiol source

In the paper

“Midodrine significantly reduces orthostatic tachycardia but to a lesser degree than intravenous saline.40”

What the sources say

• ?Not checked — no full text of the sourcecites [40] Jacob, 1997, Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia, Circulation source

In the paper

“there are several underlying diseases that can result in this syndrome, including increased sinus node automaticity, beta-adrenergic hypersensitivity, decreased parasympathetic activity, and impaired neurohumoral modulation.54”

What the sources say

• ?Not checked — no full text of the sourcecites [54] Chiale, 2006, Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac beta adrenergic receptors, Heart Rhythm source

In the paper

“by age 60, 42% of women and 32% of men will have had at least 1 vasovagal syncope, which is their cumulative incidence.65,66”

What the sources say

• ?Not checked — no full text of the sourcecites [65] Ganzeboom, 2006, Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35–60 years, J Cardiovasc Electrophysiol source
• ?Not checked — no full text of the sourcecites [66] Serletis, 2006, Vasovagal syncope in medical students and their first-degree relatives, Eur Heart J source

In the paper

“Fludrocortisone might be useful for boosting sodium retention and expanding the plasma volume, although these pharmacodynamic effects might last only 1–2 days, and its effectiveness has not been tested in randomized clinical trials.39”

What the sources say

• ?Not checked — no full text of the sourcecites [39] Rowe, 2001, Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial, JAMA source

In the paper

“The current gold standard for diagnosing syncope due to cardiac arrhythmias is recording an ECG during an episode of clinical syncope.”

In the paper

“The vasovagal response always includes hypotension and often includes bradycardia with, at times, prolonged asystole in the sinus and AV nodes.”

In the paper

“There are 4 categories of key diagnostic features: predisposing situations, prodromal symptoms, physical signs, and recovery time and symptoms.”

In the paper

“However, 2 groups have recently reported persistence of MSNA during vasovagal syncope, bringing into question the role of sympathetic activity withdrawal as the final physiologic event that precipitates loss of consciousness.85,86”

What the sources say

• ?Not checked — no full text of the sourcecites [85] Cooke, 2002, Association between vasovagal hypotension and low sympathetic neural activity during presyncope, Clin Auton Res source
• ?Not checked — no full text of the sourcecites [86] Vaddadi, 2010, Persistence of muscle sympathetic nerve activity during vasovagal syncope, Eur Heart J source

In the paper

“Although the importance of tilt testing in the investigation of patients with syncope of cardiogenic etiology is diminishing, the test continues to be helpful in clinics devoted to the care of patients with cardiovascular autonomic disorders such as autonomic neuropathy, neurogenic orthostatic hypotension, neurally mediated syncope, and POTS.”

In the paper

“However, fine and coarse myoclonic movements have been observed in approximately 10% of cases (even by untrained individuals), which can result in the condition being erroneously diagnosed as epilepsy.88”

What the sources say

• ?Not checked — no full text of the sourcecites [88] Sheldon, 2013, How to differentiate syncope from seizure, Card Electrophysiol Clin source

In the paper

“The diagnosis of vasovagal syncope is based on the clinical history, and there are abundant observational and quantitative data in this area.”

In the paper

“Furthermore, the supplemental role of tilt testing when added to medical histories reviews by experts, with or without quantitative diagnostic scores, has not been assessed, and its indications are a matter of expert consensus.101”

What the sources say

• ?Not checked — no full text of the sourcecites [101] Blanc, 2013, 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?, Prog Cardiovasc Dis source

In the paper

“- situations in which, despite careful questioning, the cause of syncope remains unclear”

In the paper

“The yield depends on the duration of monitoring and is significantly greater with implanted monitors.”

In the paper

“Patients often feel very tired for minutes to hours after the episode.”

In the paper

“Ruling out cardiac syncope is of less importance, however, for clinics specializing in providing assessment and care of patients with autonomic disorders.”

In the paper

“Tilt testing, when positive, suggests a tendency or predisposition to vasovagal syncope and does not establish it as the cause of the patient’s syncope.”

In the paper

“ILRs store ECG evidence when activated by the patient after a syncope episode and after automatic detection based on rate or rhythm criteria.”

In the paper

“When patient populations with strong presumptive evidence (ie, a high pretest probability) for vasovagal syncope are studied, the sensitivity approaches 78%-92%, and the currently recommended protocols have specificities of approximately 90% compared with the response of asymptomatic patients.”

In the paper

“The vasovagal reflex is often triggered by adjunctive agents such as isoproterenol, nitrates, and clomipramine.”

In the paper

“In most cardiology settings, it is important to determine whether the patients’ syncope is caused by arrhythmia.”

In the paper

“The usefulness of investigation strategies depends on the patient mix and the purpose of the investigation.”

In the paper

“Prodromal features include progressive presyncope, diaphoresis, a sense of warmth, flushing, nausea, abdominal discomfort, visual blurring, and vision loss.”

In the paper

“However, a syncopal episode associated with a normal sinus rhythm can be due to several disorders such as orthostatic hypotension, vasovagal and carotid sinus reflexes, and even pseudosyncope.”

In the paper

“Depending on the method, most patients with probable vasovagal syncope develop presyncope or syncope, while most control patients do not.”

In the paper

“The age differences among these reports suggest that a failure of venous return could be the main factor in older patients, while younger patients might also have active vasodilation.”

In the paper

“A positive response is defined as clinically reminiscent presyncope or syncope associated with hypotension and usually bradycardia.”

In the paper

“Pseudosyncope is a poorly reported syndrome of apparent syncopal episodes in the absence of cerebral hypoperfusion or hemodynamic changes that might cause cerebral hypoperfusion.”

In the paper

“Although these scores report overall high degrees of accuracy, they likely require revision and validation in larger populations.”

In the paper

““Prolonged” can mean as little as 2–3 minutes, and the time period is a key feature distinguishing vasovagal syncope from initial orthostatic hypotension.”

In the paper

“External monitors have a loop memory that continuously records and deletes the ECGs, storing them when activated.”

In the paper

“The devices are implanted subcutaneously under local anesthesia and last up to 3 years.”

In the paper

“Unconsciousness usually lasts less than 1–2 minutes, but full recovery can be sluggish.”

In the paper

“The tilt test can prove useful for elderly patients due to the difficulties in obtaining an informative history in some older patients and due to its usefulness in identifying the cause of unexplained falls. 99,100”

What the sources say

• ?Not checked — no full text of the sourcecites [99] Del Rosso, 2008, Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score, Heart source
• ?Not checked — no full text of the sourcecites [100] Rafanelli, 2014, Clinical aspects and diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls, Aging Clin Exp Res source

In the paper

“Fainting usually occurs after prolonged standing or sitting but can be triggered even in the supine position by exposure to medical or dental situations, pain, and scenes of injury.”

In the paper

“The trials studied children, used tilt test outcomes as the main measure, studied extraordinarily symptomatic patients, or were open label.”

In the paper

“Tilt training has 2 forms. In the first, patients start training using repetitive tilt tests under monitored conditions. In the second, patients simply practice standing quietly at home for prolonged periods of time.”

In the paper

“In the Prevention of Syncope Trial (POST) study,91 patients with no syncope in the previous year had a 7% likelihood of fainting in the next year, while those with at least 1 syncope had a 40% likelihood of fainting.68”

What the sources say

• ?Not checked — no full text of the sourcecites [68] Sumner, 2010, Prevention of Syncope Trial I. Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden, J Cardiovasc Electrophysiol source

In the paper

“The POST 2 trial compared fludrocortisone to placebo in patients with recurrent, apparent, vasovagal syncope and showed only a strong trend to treatment benefit.”

In the paper

“This treatment is hampered by poor patient compliance when conducting the program for an extended period of time and by an as yet undetermined biologic mechanism.”

In the paper

“Younger and older individuals differ markedly, with the latter group more likely to have complicating comorbidities and medical therapies than the former group.”

In the paper

“Compared with conventional approaches, external ECG monitors provide more and earlier diagnoses and are cost effective.”

In the paper

“The major limitations of midodrine are the need for frequent dosing, its effects on supine hypertension, and a lack of knowledge of its teratogenic effects.”

In the paper

“While the former might be beneficial, the latter is not.114”

What the sources say

• ?Not checked — no full text of the sourcecites [114] Kuriachan, 2008, Evidence-based treatment for vasovagal syncope, Heart Rhythm source

In the paper

“The trial has not undergone peer review and has not been published.”

In the paper

“Furthermore, only the most motivated patients will commit to medical therapy to prevent a handful of yearly syncopal episodes.”

In the paper

“Patients with unexplained syncope have low plasma adenosine levels, and exogenous injections with adenosine triphosphate or adenosine can cause transient complete heart block in these patients more often than in control patients.”

In the paper

“However, this apparently beneficial response is also seen ubiquitously in single-blind adult trials, a response that is not reproduced in properly conducted double-blind trials.”

In the paper

“However, no comparisons between conventional single-chamber and dual-chamber pacing have been conducted.”