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

May combine two claims.

Implantable loop recorders improve care only in the subset of patients who are older, have asystole documented on the recorder, and had negative tilt test results, probably because many diagnoses are vasovagal syncope.

“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.”

• cites [105] Krahn, 1995, The etiology of syncope in patients with negative tilt table and electrophysiological testing, Circulation sourceNot checked — no full text of the source
• cites [106] Krahn, 1999, Use of an extended monitoring strategy in patients with problematic syncope. Reveal Investigators, Circulation sourceDisputed

  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.

  Experimental — accuracy not yet measured
• 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 sourcePartly 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)

  Experimental — accuracy not yet measured
• cites [108] Moya, 2008, Reproducibility of electrocardiographic findings in patients with suspected reflex neurally-mediated syncope, Am J Cardiol sourceNot checked — no full text of the source
• cites [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 sourceNot checked — no full text of the source
• cites [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 sourceNot checked — no full text of the source
• cites [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 sourceNot checked — no full text of the source
• 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 sourcePartly 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)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

More than 75% of POTS patients are female.

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

• cites [7] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc sourceNot checked — no full text of the source
• cites [8] Schondorf, 1993, Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?, Neurology sourceNot checked — no full text of the source
• cites [9] Low, 1995, Postural tachycardia syndrome (POTS), NeurologyNot matched

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

• cites [11] Singer, 2012, Postural tachycardia in children and adolescents: what is abnormal?, J Pediatr sourceSupported
• cites [12] Garland, 2007, The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome, Neurology sourceNot checked — no full text of the source
• cites [13] Low, 2009, Postural tachycardia syndrome (POTS), J Cardiovasc Electrophysiol sourceSupported
• cites [14] Robertson, 1999, The epidemic of orthostatic tachycardia and orthostatic intolerance, Am J Med Sci sourceNot checked — no full text of the source
• cites [16] Freeman, 2011, Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome, Clin Auton Res sourceNot checked — no full text of the source

May combine two claims.

A sudden fall in venous return lowers cardiac output and blood pressure, which baroreceptors sense and which triggers sympathetic vasoconstriction and venoconstriction with a rise in heart rate.

“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”

• cites [73] Mosqueda-Garcia, 2000, The elusive pathophysiology of neurally mediated syncope, Circulation sourcePartly 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)

  Experimental — accuracy not yet measured

May combine two claims.

Mechanisms described in POTS include autonomic denervation, hypovolemia, hyperadrenergic stimulation, deconditioning, and hypervigilance.

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

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

May combine two claims.

Low-dose oral propranolol (10-20 mg) acutely lowers standing heart rate and improves POTS symptoms, while higher doses are less well tolerated.

“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”

• cites [42] Raj, 2009, Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more, Circulation sourcePartly 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)

  Experimental — accuracy not yet measured

May combine two claims.

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

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

• 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 sourcePartly 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)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Treadmill exercise testing may help document an exaggerated tachycardic response to exertion, but this has not been validated.

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

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

May combine two claims.

Pyridostigmine blunts orthostatic tachycardia and can improve chronic symptoms, but it is limited by adverse effects including diarrhea, abdominal pain or cramps, nausea, and increased urinary urgency and frequency.

“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”

• cites [45] Raj, 2005, Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome, Circulation sourcePartly 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)

  Experimental — accuracy not yet measured
• cites [46] Kanjwal, 2011, Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience, Pacing Clin Electrophysiol sourceNot checked — no full text of the source

May combine two claims.

Deconditioned POTS patients have reduced left ventricular mass, stroke volume, and blood volume, and these improve with exercise training.

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

• cites [35] Fu, 2010, Cardiac origins of the postural orthostatic tachycardia syndrome, J Am Coll Cardiol sourcePartly 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)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

For many years, vasovagal syncope was believed to result from loss of peripheral sympathetic activity, with blunting or cessation of muscle sympathetic nerve activity as the proposed mechanism.

“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”

• cites [82] Morillo, 1997, Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope, Circulation sourceNot checked — no full text of the source
• cites [83] Mosqueda-Garcia, 1997, Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt, J Clin Invest sourceSupported
• cites [84] Jardine, 2002, Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope, Am J Physiol Heart Circ Physiol sourceNot checked — no full text of the source

May combine two claims.

During orthostatic vasovagal syncope, the initial fall in blood pressure is driven by a roughly 50% decrease in cardiac output, and concurrent vasodilation occurs in only some patients.

“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”

• cites [78] Verheyden, 2008, Steep fall in cardiac output is main determinant of hypotension during drug-free and nitroglycerine-induced orthostatic vasovagal syncope, Heart Rhythm sourceNot checked — no full text of the source
• cites [79] Gisolf, 2004, Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response, J Am Coll Cardiol sourceNot checked — no full text of the source
• cites [80] Verheyden, 2007, Impact of age on the vasovagal response provoked by sublingual nitroglycerine in routine tilt testing, Clin Sci sourcePartly 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)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Vasovagal syncope diagnostic scores serve as useful reminders of diagnostic points and provide reproducible criteria for entry into observational, genetic, and randomized controlled interventional trials.

“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”

• cites [91] Sheldon, 2006, Diagnostic criteria for vasovagal syncope based on a quantitative history, Eur Heart J sourceNot checked — no full text of the source
• cites [96] Alboni, 2001, Diagnostic value of history in patients with syncope with or without heart disease, J Am Coll Cardiol sourcePartly 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)

  Experimental — accuracy not yet measured
• cites [97] Sud, 2009, Predicting the cause of syncope from clinical history in patients undergoing prolonged monitoring, Heart Rhythm sourceNot checked — no full text of the source

May combine two claims.

Before presyncope begins, sympathetic vasoconstriction and baroreflex sensitivity are well preserved, and muscle sympathetic nerve activity withdrawal occurs late after hypotension starts.

“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.”

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

  Experimental — accuracy not yet measured

May combine two claims.

Muscle sympathetic nerve activity was normal in the normal blood pressure phenotype and increased in the low blood pressure phenotype.

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

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

May combine two claims.

Both phenotypes have reduced norepinephrine availability, which ultimately impairs the neurocirculatory response to orthostatic stress.

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

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

May combine two claims.

Fu and Levine found a moderate cardiac output decline with vasodilation in most presyncope participants, while a minority had no total peripheral resistance change during presyncope.

“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.”

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

May combine two claims.

In some vasovagal syncope patients, reduced preload is not the main cause of symptoms, and peripheral vasodilation is important instead.

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

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

  Experimental — accuracy not yet measured

May combine two claims.

Based on this evidence, there have been several observational studies and three small randomized trials of serotonin transport inhibitors for prevention of vasovagal syncope.

“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”

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

  Experimental — accuracy not yet measured
• 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 sourceSupported

May combine two claims.

Earlier observational, open-label, and single-blind pacing studies were uniformly positive, but two subsequent double-blind studies in adults were negative.

“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”

• cites [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 sourceNot checked — no full text of the source
• 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 sourcePartly 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)

  Experimental — accuracy not yet measured
• cites [135] Ammirati, 2001, Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial, Circulation sourcePartly 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)

  Experimental — accuracy not yet measured
• cites [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 sourceNot checked — no full text of the source
• 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 sourcePartly 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)

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

  Experimental — accuracy not yet measured

May combine two claims.

In that trial, syncope recurred in a substantial minority of patients, and the study was open label.

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

• 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 sourcePartly 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)

  Experimental — accuracy not yet measured

May combine two claims.

Results of lifestyle and medical therapies have generally been positive in uncontrolled and short-term controlled trials, but long-term placebo-controlled prospective trials have been less encouraging.

“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.”

• cites [113] Sutton, 2012, Key challenges in the current management of syncope, Nat Rev Cardiol sourceNot checked — no full text of the source
• cites [114] Kuriachan, 2008, Evidence-based treatment for vasovagal syncope, Heart Rhythm sourceNot checked — no full text of the source
• cites [115] Vyas, 2013, Are treatments for vasovagal syncope effective? A meta-analysis, Int J Cardiol sourceNot checked — no full text of the source
• cites [116] Brignole, 2003, Management of syncope referred urgently to general hospitals with and without syncope units, Europace sourceCould 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)

  Experimental — accuracy not yet measured
• cites [117] Sutton, 2013, Treatment of reflex syncope, J Med Diagn Meth sourceNot checked — no full text of the source

May combine two claims.

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

“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”

• 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 sourceSupported

May combine two claims.

A recent ISSUE-3 subanalysis showed that syncope recurrence for patients with asystole, with or without syncope, was 5% with negative tilt test results and 55% with positive tilt test results, similar to controls without pacing.

“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”

• 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 sourcePartly 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)

  Experimental — accuracy not yet measured

May combine two claims.

The 10-minute standing tests for POTS provided reasonable accuracy in a small adult study, but have not been validated for pediatric populations.

“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”

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

May combine two claims.

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

“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”

• cites [11] Singer, 2012, Postural tachycardia in children and adolescents: what is abnormal?, J Pediatr sourcePartly 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)

  Experimental — accuracy not yet measured

May combine two claims.

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

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

• cites [142] McLeod, 1999, Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures, Heart sourcePartly 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)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Most POTS patients first present between ages 15 and 25 years.

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

• cites [7] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

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

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

Classified as probably not a substantial claim. May combine two claims.

Recommendations were based on published evidence as much as possible, with the highest-level evidence included for each section.

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

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

POTS symptoms occur with standing, are not tied to particular postures, and include systemic features such as fatigue, sleep disturbance, and migraine.

“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”

• cites [7] Thieben, 2007, Postural orthostatic tachycardia syndrome: the Mayo clinic experience, Mayo Clin Proc sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The document's recommendations and definitions were based on consensus of the full writing group following the Heart Rhythm Society process for consensus-based clinical guidance.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

POTS prevalence is about 0.2%, with little variation across four published reports.

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

• cites [9] Low, 1995, Postural tachycardia syndrome (POTS), NeurologyNot checked yet

  Not checked in the free run.

• cites [12] Garland, 2007, The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome, Neurology sourceNot checked — no full text of the source
• cites [14] Robertson, 1999, The epidemic of orthostatic tachycardia and orthostatic intolerance, Am J Med Sci sourceNot checked — no full text of the source
• cites [15] Schondorf, 1999, Orthostatic intolerance in the chronic fatigue syndrome, J Auton Nerv Syst sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

All writing group members and peer reviewers provided conflict-of-interest disclosure statements.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

POTS is a systemic illness in which postural tachycardia is only one of several criteria.

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

Classified as probably not a substantial claim.

Consensus was identified by surveys of the entire writing group with a predefined agreement threshold of more than 75% for each recommendation.

“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.”

May combine two claims.

POTS and IST can present similarly, but IST is triggered by both physiologic and emotional stress, whereas POTS is generally triggered only by orthostatic stress.

“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.”

May combine two claims.

The median age of first syncope is about 14 years, and most people with VVS have their first syncope before age 40.

“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”

• cites [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 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

About 35% of emergency department patients with syncope remain undiagnosed.

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

Classified as probably not a substantial claim.

Tilt-table testing can provide vital signs over longer periods than a simple stand test.

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

May combine two claims.

Sinus node modification or ablation for IST has reasonably good primary success rates but high symptom recurrence and significant complication rates.

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

Classified as probably not a substantial claim. May combine two claims.

POTS treatment is difficult, no therapy is uniformly successful, and combinations of approaches are often needed.

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

May combine two claims.

The overall 1-year recurrence rate of VVS is about 25%-35% and can be predicted by the number of syncopes in the prior year.

“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”

• cites [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 sourceNot checked — no full text of the source

May combine two claims.

Hyperadrenergic POTS patients are hypersensitive to isoproterenol and have marked tachycardia at doses that do not alter hemodynamics in healthy people.

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

• cites [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 sourceNot checked — no full text of the source

May combine two claims.

Radiofrequency sinus node modification for POTS sinus tachycardia often worsens symptoms and occasionally leads to pacemaker requirement.

“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”

• cites [50] Shen, 2001, Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?, Pacing Clin Electrophysiol sourceNot checked — no full text of the source

May combine two claims.

Expert centers report anecdotally that 1 L of normal saline over 1 hour reduces orthostatic tachycardia and improves symptoms for several hours to 2 days.

“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”

• cites [40] Jacob, 1997, Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia, Circulation sourceNot checked — no full text of the source
• cites [41] Gordon, 2000, Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome, Clin Auton Res sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

About 30%-50% of syncope patients are diagnosed with an autonomically mediated form, and most of these are vasovagal.

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

May combine two claims.

Complications of sinus node modification or ablation for IST include permanent pacing, transient or permanent phrenic nerve paralysis, and transient superior vena cava syndrome.

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

May combine two claims.

Hyperadrenergic POTS occurs in up to 50% of patients and is associated with a standing systolic blood pressure rise of at least 10 mm Hg over 10 minutes and standing plasma norepinephrine of at least 600 pg/mL.

“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.”

May combine two claims.

Physiologic and psychometric studies indicate that anxiety is common in POTS but does not cause the orthostatic heart rate response, which reflects an underlying physiologic abnormality.

“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.”

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

May combine two claims.

Midodrine significantly reduces orthostatic tachycardia, though less than intravenous saline.

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

• cites [40] Jacob, 1997, Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia, Circulation sourceNot checked — no full text of the source

May combine two claims.

Underlying conditions that can produce IST include increased sinus node automaticity, beta-adrenergic hypersensitivity, reduced parasympathetic activity, and impaired neurohumoral modulation.

“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”

• cites [54] Chiale, 2006, Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac beta adrenergic receptors, Heart Rhythm sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

By age 60, 42% of women and 32% of men have had at least one vasovagal syncope.

“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”

• cites [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 sourceNot checked — no full text of the source
• cites [66] Serletis, 2006, Vasovagal syncope in medical students and their first-degree relatives, Eur Heart J sourceNot checked — no full text of the source

May combine two claims.

Fludrocortisone may boost sodium retention and expand plasma volume, but its effects may last only 1-2 days and its effectiveness has not been tested in randomized trials.

“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”

• cites [39] Rowe, 2001, Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial, JAMA sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

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

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

May combine two claims.

The vasovagal response always includes hypotension and often includes bradycardia, sometimes with prolonged sinus or AV nodal asystole.

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

Probably not a substantial claim: may not pass S3 (load-bearing).

Four categories of key diagnostic features exist for vasovagal syncope: predisposing situations, prodromal symptoms, physical signs, and recovery time and symptoms.

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

May combine two claims.

Two groups recently reported that muscle sympathetic nerve activity persists during vasovagal syncope, which questions whether sympathetic withdrawal is the final event causing loss of consciousness.

“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”

• cites [85] Cooke, 2002, Association between vasovagal hypotension and low sympathetic neural activity during presyncope, Clin Auton Res sourceNot checked — no full text of the source
• cites [86] Vaddadi, 2010, Persistence of muscle sympathetic nerve activity during vasovagal syncope, Eur Heart J sourceNot checked — no full text of the source

May combine two claims.

The importance of tilt testing in investigating syncope of cardiogenic etiology is diminishing, but it remains helpful in clinics for cardiovascular autonomic disorders such as autonomic neuropathy, neurogenic orthostatic hypotension, neurally mediated syncope, and POTS.

“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.”

May combine two claims.

Fine and coarse myoclonic movements occur in about 10% of vasovagal syncope cases and can lead to an erroneous diagnosis of epilepsy.

“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”

• cites [88] Sheldon, 2013, How to differentiate syncope from seizure, Card Electrophysiol Clin sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The diagnosis of vasovagal syncope rests on clinical history, and abundant observational and quantitative data exist in this area.

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

May combine two claims.

The supplemental role of tilt testing added to expert medical history review, with or without quantitative diagnostic scores, has not been assessed, and its indications are a matter of expert consensus.

“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”

• cites [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 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Tilt-table testing can help when the cause of syncope remains unclear despite careful questioning.

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

May combine two claims.

The diagnostic yield of ECG monitoring depends on monitoring duration and is significantly greater with implanted monitors.

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

Probably not a substantial claim: may not pass S3 (load-bearing).

Patients often feel very tired for minutes to hours after a vasovagal syncope episode.

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

Probably not a substantial claim: may not pass S3 (load-bearing).

Ruling out cardiac syncope is less important in clinics that specialize in assessing and caring for patients with autonomic disorders.

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

May combine two claims.

A positive tilt test suggests a tendency or predisposition to vasovagal syncope and does not establish it as the cause of the patient's syncope.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Implantable loop recorders store ECG evidence when activated by the patient after a syncope episode and after automatic detection based on rate or rhythm criteria.

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

May combine two claims.

In populations with high pretest probability for vasovagal syncope, tilt-test sensitivity approaches 78%-92%, and currently recommended protocols have specificities of about 90% compared with asymptomatic patients.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing).

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

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

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

In most cardiology settings, determining whether syncope is caused by arrhythmia is important.

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

Probably not a substantial claim: may not pass S4 (based).

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

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

Probably not a substantial claim: may not pass S3 (load-bearing).

Prodromal features of vasovagal syncope include progressive presyncope, sweating, warmth, flushing, nausea, abdominal discomfort, visual blurring, and vision loss.

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

Probably not a substantial claim: may not pass S3 (load-bearing).

A syncopal episode with normal sinus rhythm can be due to several disorders, including orthostatic hypotension, vasovagal and carotid sinus reflexes, and pseudosyncope.

“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.”

May combine two claims.

Depending on the method, most patients with probable vasovagal syncope develop presyncope or syncope during tilt testing, while most control patients do not.

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

May combine two claims.

Age differences across reports suggest that venous return failure may be the main factor in older vasovagal syncope patients, while younger patients may also have active vasodilation.

“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.”

Classified as probably not a substantial claim.

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

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

Probably not a substantial claim: may not pass S3 (load-bearing).

Pseudosyncope is a poorly reported syndrome of apparent syncopal episodes without cerebral hypoperfusion or hemodynamic changes that might cause cerebral hypoperfusion.

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

May combine two claims.

Although vasovagal syncope diagnostic scores report high overall accuracy, they likely need revision and validation in larger populations.

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

Classified as probably not a substantial claim. May combine two claims.

In this context, prolonged can mean as little as 2-3 minutes, and this time period is a key feature that distinguishes vasovagal syncope from initial orthostatic hypotension.

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

Probably not a substantial claim: may not pass S3 (load-bearing).

External ECG monitors have loop memory that continuously records and deletes ECGs, storing them when activated.

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

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Implantable loop recorders are implanted subcutaneously under local anesthesia and last up to 3 years.

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

May combine two claims.

Unconsciousness in vasovagal syncope usually lasts less than 1-2 minutes, but full recovery can be slow.

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

May combine two claims.

Tilt testing can be useful in elderly patients because obtaining an informative history can be difficult and because it can help identify the cause of unexplained falls.

“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”

• cites [99] Del Rosso, 2008, Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score, Heart sourceNot checked — no full text of the source
• cites [100] Rafanelli, 2014, Clinical aspects and diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls, Aging Clin Exp Res sourceNot checked — no full text of the source

May combine two claims.

Fainting in vasovagal syncope usually follows prolonged standing or sitting, but can also be triggered while supine by medical or dental situations, pain, or scenes of injury.

“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.”

May combine two claims.

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

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

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Tilt training has two forms: repetitive tilt tests under monitored conditions, and standing quietly at home for prolonged periods.

“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.”

May combine two claims.

In the Prevention of Syncope Trial, patients with no syncope in the previous year had a 7% likelihood of fainting in the next year, while those with at least one syncope had a 40% likelihood.

“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”

• cites [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 sourceNot checked — no full text of the source

May combine two claims.

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

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

May combine two claims.

Tilt training is hampered by poor patient compliance over extended periods and by an undetermined biologic mechanism.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Younger and older individuals differ markedly, with older patients more likely to have complicating comorbidities and medical therapies.

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

May combine two claims.

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

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

May combine two claims.

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

“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.”

May combine two claims.

The monitored repetitive tilt-test form of tilt training might be beneficial, while the home standing form is not.

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

• cites [114] Kuriachan, 2008, Evidence-based treatment for vasovagal syncope, Heart Rhythm sourceNot checked — no full text of the source

May combine two claims.

The POST 2 trial has not undergone peer review and has not been published.

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

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

Only the most motivated patients will commit to medical therapy to prevent a handful of yearly syncopal episodes.

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

May combine two claims.

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

“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.”

May combine two claims.

The apparently beneficial response to pacing is also seen ubiquitously in single-blind adult trials, but is not reproduced in properly conducted double-blind trials.

“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.”

Probably not a substantial claim: may not pass S3 (load-bearing).

No comparisons between conventional single-chamber and dual-chamber pacing have been conducted.

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

May combine two claims.

Documentation of a prolonged asystolic reflex during tilt-table testing predicts a similar response during spontaneous syncope, but the benefit of pacing for tilt-positive cardioinhibitory syncope remains unproven.

“Although the documentation of a prolonged asystolic reflex during tilt-table testing predicts a similar response during spontaneous syncope, the benefit of pacing for patients with tilt-positive cardioinhibitory syncope remains unproven.111”

• cites [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 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Symptoms from vasovagal syncope are usually more clearly articulated in young patients than in much older adults, and establishing the diagnosis is usually straightforward.

“Symptoms resulting from vasovagal syncope are usually more clearly articulated in young patients than in much older adults, and establishing the diagnosis is usually straightforward.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Relatively little is known about the natural history of these three syndromes, although they are widely suspected to be chronic disorders with waxing and waning severity.

“There is relatively little known about the natural history of these 3 syndromes, although it is widely suspected that they are chronic disorders with waxing and waning severity.”

Classified as probably not a substantial claim. May combine two claims.

Because medical history usually provides a clear diagnosis and tilt testing has imperfect sensitivity and specificity in pediatric patients, tilt testing is usually not indicated.

“Given that the medical history usually provides a clear diagnosis and that tilt testing has imperfect sensitivity and specificity in pediatric patients, such testing is usually not indicated.”

May combine two claims.

There is little evidence that any treatment helps children with vasovagal syncope or POTS, and physicians rely on insights from adult medical literature.

“There is little evidence that any treatment helps children with vasovagal syncope or POTS, and physicians rely on insights from adult medical literature.”

May combine two claims.

Syncope during exercise usually raises concern about a rare cardiac electrical or structural cause, but the most common cause of exercise-related syncope in pediatric populations is still vasovagal syncope.

“Syncope during exercise usually raises concern about a rare cardiac electrical or structural cause, but the most common cause of exercise-related syncope in pediatric populations is still vasovagal syncope.144”

• cites [144] Colivicchi, 2002, Exercise-related syncope in young competitive athletes without evidence of structural heart disease. Clinical presentation and long-term outcome, Eur Heart J sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Portable beat-to-beat blood pressure monitors are lacking.

“We lack portable, beat-to-beat blood pressure monitors, and these could easily be integrated into current and cutting-edge technologies.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Dual-chamber pacing was used in almost all the above-mentioned trials, with a rate-drop response feature that initiated rapid dual-chamber pacing if the device detected a rapid heart rate decrease.

“Dual-chamber pacing was used in almost all the above-mentioned trials, with a rate-drop response feature in the pacemaker that instituted rapid dual-chamber pacing if the device detected a rapid decrease in heart rate.”

May combine two claims.

This syncope is not thought to be due to the vasovagal reflex but is included because the population shares clinical features with vasovagal syncope patients.

“This syncope is not thought to be due to the vasovagal reflex but is included because the population with this type of syncope shares clinical features with those who have vasovagal syncope.”

May combine two claims.

Tilt-table testing can be performed to assess hypotensive susceptibility and identify patients who might not respond to permanent cardiac pacing.

“Accordingly, tilt-table testing can be performed to assess hypotensive susceptibility and identify patients who might not respond to permanent cardiac pacing.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Pseudosyncope should be suspected when patients present with very frequent, at least daily, or prolonged syncope with symptoms similar to vasovagal syncope.

“Pseudosyncope should be suspected when patients present with very frequent (at least daily) or prolonged syncope, with similar symptoms to vasovagal syncope.”

Classified as probably not a substantial claim.

There is still a large gap in understanding the causes of the physiologic disturbances underlying these syndromes.

“There is still a large gap in our understanding of the causes of the physiologic disturbances underlying these syndromes.”

Probably not a substantial claim: may not pass S4 (based).

Despite professional guidelines, there is little evidence on the optimum strategy for assessing patients who might have these disorders.

“Similarly and despite professional guidelines, there is little evidence on the optimum strategy for assessing patients who might have these disorders.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The fact that many young patients appear to stop fainting in late adolescence dulls enthusiasm for specific medical treatment of young people, particularly pacemakers.

“This fact dulls enthusiasm for specific medical treatment of young people, particularly the use of pacemakers.”

• AssumptionRests on an assumption: Many young patients with vasovagal syncope or POTS stop fainting in late adolescence.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

None of these syndromes have investigative approaches that make much use of recent advances in information technology in medical care.

“None of the syndromes have investigative approaches that make much use of recent advances in information technology in medical care.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Many of these patients also have an earlier history of bona fide vasovagal syncope, and untangling the medical history requires particular care.

“Many of these patients also have an earlier history of bona fide vasovagal syncope, and untangling the medical history requires particular care.”

May combine two claims.

Although medical history is the cornerstone for diagnosing pediatric POTS, an orthostatic test is required to confirm the diagnosis.

“Although the cornerstone for the diagnosis of pediatric POTS is the medical history, an orthostatic test is required to confirm the diagnosis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The relatively limited pediatric literature means that most insights and treatments for POTS and vasovagal syncope have come from adult medical literature.

“The relatively limited pediatric literature on this topic has meant that most insights and treatments for POTS and vasovagal syncope have come from the adult medical literature.”

May combine two claims.

During follow-up, the 2-year estimated syncope recurrence rate was 57% with the pacemaker off and 25% with the pacemaker on, a relative risk reduction of 57%.

“During follow-up, the 2-year estimated syncope recurrence rate was 57% with the pacemaker off and 25% with the pacemaker on, with a relative risk reduction of 57%.”

• cites [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 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

An ECG is a simple and well-tolerated test to screen for relatively uncommon but dangerous causes of syncope, including myocarditis, inheritable cardiomyopathies, long QT, and other inherited or acquired arrhythmia causes.

“An ECG is a simple and well-tolerated test to screen for relatively uncommon but dangerous causes of syncope, including myocarditis, inheritable cardiomyopa-thies, long QT, and other inherited or acquired causes of arrhythmia.”