Syncope Diagnosis at Referral to a Tertiary Syncope Unit: An in-Depth Analysis of the FAST II.

OBJECTIVE: A substantial number of patients with a transient loss of consciousness (T-LOC) are referred to a tertiary syncope unit without a diagnosis. This study investigates the final diagnoses reached in patients who, on referral, were undiagnosed or inaccurately diagnosed in secondary care. METHODS: This study is an in-depth analysis of the recently published Fainting Assessment Study II, a prospective cohort study in a tertiary syncope unit. The diagnosis at the tertiary syncope unit was established after history taking (phase 1), following autonomic function tests (phase 2), and confirming after critical follow-up of 1.5-2 years, with the adjudicated diagnosis (phase 3) by a multidisciplinary committee. Diagnoses suggested by the referring physician were considered the phase 0 diagnosis. We determined the accuracy of the phase 0 diagnosis by comparing this with the phase 3 diagnosis. RESULTS: 51% (134/264) of patients had no diagnosis upon referral (phase 0), the remaining 49% (130/264) carried a diagnosis, but 80% (104/130) considered their condition unexplained. Of the patients undiagnosed at referral, three major causes of T-LOC were revealed: reflex syncope (69%), initial orthostatic hypotension (20%) and psychogenic pseudosyncope (13%) (sum > 100% due to cases with multiple causes). Referral diagnoses were either inaccurate or incomplete in 65% of the patients and were mainly altered at tertiary care assessment to reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. A diagnosis of cardiac syncope at referral proved wrong in 17/18 patients. CONCLUSIONS: Syncope patients diagnosed or undiagnosed in primary and secondary care and referred to a syncope unit mostly suffer from reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. These causes of T-LOC do not necessarily require ancillary tests, but can be diagnosed by careful history-taking. Besides access to a network of specialized syncope units, simple interventions, such as guideline-based structured evaluation, proper risk-stratification and critical follow-up may reduce diagnostic delay and improve diagnostic accuracy for syncope.

Diagnosis and treatment of orthostatic hypotension.

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.

[Transient loss of consciousness]. / Wegrakingen.

Although transient loss of consciousness (TLOC) is a common problem, hospital care for patients with TLOC is characterised by high rates of no diagnosis and misdiagnosis, accompanied by unnecessary hospital admissions and tests. We attribute these problems to increasing specialisation as well as to a blind spot for vasovagal syncope, a condition not claimed by any specialty. We suggest that all doctors seeing patients with TLOC, both in primary and secondary care, should be familiar with the presentations of the relatively harmless vasovagal syncope and the alarm symptoms of potentially life-threatening cardiac syncope. In this article we present some practical pointers to recognise these conditions and answer some frequently-asked questions regarding the diagnosis and treatment of TLOC.

Diagnostic criteria for initial orthostatic hypotension: a narrative review.

Abnormalities in orthostatic blood pressure changes upon active standing are associated with morbidity, mortality, and reduced quality of life. However, over the last decade, several population-based cohort studies have reported a remarkably high prevalence (between 25 and 70%) of initial orthostatic hypotension (IOH) among elderly individuals. This has raised the question as to whether the orthostatic blood pressure patterns in these community-dwelling elderly should truly be considered as pathological. If not, redefining of the systolic cutoff values for IOH (i.e., a value ≥ 40 mmHg in systolic blood pressure in the first 15 s after standing up) might be necessary to differ between normal aging and true pathology. Therefore, in this narrative review, we provide a critical analysis of the current reference values for the changes in systolic BP in the first 60 s after standing up and discuss how these values should be applied to large population studies. We will address factors that influence the magnitude of the systolic blood pressure changes following active standing and the importance of standardization of the stand-up test, which is a prerequisite for quantitative, between-subject comparisons of the postural hemodynamic response.

Systemic and cerebral circulatory adjustment within the first 60 s after active standing: An integrative physiological view.

Transient cardiovascular and cerebrovascular responses within the first minute of active standing provide the means to assess autonomic, cardiovascular and cerebrovascular regulation using a real-world everyday stimulus. Traditionally, these responses have been used to detect autonomic dysfunction, and to identify the hemodynamic correlates of patient symptoms and attributable causes of (pre)syncope and falls. This review addresses the physiology of systemic and cerebrovascular adjustment within the first 60 s after active standing. Mechanical factors induced by standing up cause a temporal mismatch between cardiac output and vascular conductance which leads to an initial blood pressure drops with a nadir around 10 s. The arterial baroreflex counteracts these initial blood pressure drops, but needs 2-3 s to be initiated with a maximal effect occurring at 10 s after standing while, in parallel, cerebral autoregulation buffers these changes within 10 s to maintain adequate cerebral perfusion. Interestingly, both the magnitude of the initial drop and these compensatory mechanisms are thought to be quite well-preserved in healthy aging. It is hoped that the present review serves as a reference for future pathophysiological investigations and epidemiological studies. Further experimental research is needed to unravel the causal mechanisms underlying the emergence of symptoms and relationship with aging and adverse outcomes in variants of orthostatic hypotension.

Diagnostic yield and accuracy in a tertiary referral syncope unit validating the ESC guideline on syncope: a prospective cohort study.

AIMS: To assess in patients with transient loss of consciousness the diagnostic yield, accuracy, and safety of the structured approach as described in the ESC guidelines in a tertiary referral syncope unit. METHODS AND RESULTS: Prospective cohort study including 264 consecutive patients (≥18 years) referred with at least one self-reported episode of transient loss of consciousness and presenting to the syncope unit between October 2012 and February 2015. The study consisted of three phases: history taking (Phase 1), autonomic function tests (AFTs) (Phase 2), and after 1.5-year follow-up with assessment by a multidisciplinary committee (Phase 3). Diagnostic yield was assessed after Phases 1 and 2. Empirical diagnostic accuracy was measured for diagnoses according to the ESC guidelines after Phase 3. The diagnostic yield after Phase 1 (history taking) was 94.7% (95% CI: 91.1-97.0%, 250/264 patients) and increased to 97.0% (93.9-98.6%, 256/264 patients) after Phase 2. The overall diagnostic accuracy (as established in Phase 3) of the Phases 1 and 2 diagnoses was 90.6% (95% CI: 86.2-93.8%, 232/256 patients). No life-threatening conditions were missed. Three patients died, two unrelated to the cause of transient loss of consciousness, and one whom remained undiagnosed. CONCLUSION: A clinical work-up at a tertiary syncope unit using the ESC guidelines has a high diagnostic yield, accuracy, and safety. History taking (Phase 1) is the most important diagnostic tool. Autonomic function tests never changed the Phase 1 diagnosis but helped to increase the certainty of the Phase 1 diagnosis in many patients and yield additional diagnoses in patients who remained undiagnosed after Phase 1. Diagnoses were inaccurate in 9.4%, but no serious conditions were missed. This is adequate for clinical practice.

Diagnostic accuracy of evaluation of suspected syncope in the emergency department: usual practice vs. ESC guidelines.

BACKGROUND: Syncope is a frequent reason for referral to the emergency department. After excluding a potentially life-threatening condition, the second objective is to find the cause of syncope. The objective of this study was to assess the diagnostic accuracy of the treating physician in usual practice and to compare this to the diagnostic accuracy of a standardised evaluation, consisting of thorough history taking and physical examination by a research physician. METHODS: This prospective cohort study included suspected (pre) syncope patients without an identified serious underlying condition who were assessed in the emergency department. Patients were initially seen by the initial treating physician and the usual evaluation was performed. A research physician, blinded to the findings of the initial treating physician, then performed a standardised evaluation according to the ESC syncope guidelines. Diagnostic accuracy (proportion of correct diagnoses) was determined by expert consensus after long-term follow-up. RESULTS: One hundred and one suspected (pre) syncope patients were included (mean age 59 ± 20 years). The usual practice of the initial treating physicians did not in most cases follow ESC syncope guidelines, with orthostatic blood pressure measurements made in only 40% of the patients. Diagnostic accuracy by the initial treating physicians was 65% (95% CI 56-74%), while standardised evaluation resulted in a diagnostic accuracy of 80% (95% CI 71-87%; p = 0.009). No life-threatening causes were missed. CONCLUSIONS: Usual practice of the initial treating physician resulted in a diagnostic accuracy of 65%, while standardised practice, with an emphasis on thorough history taking, increased diagnostic accuracy to 80%. Results suggest that the availability of additional resources does not result in a higher diagnostic accuracy than standardised evaluation, and that history taking is the most important diagnostic test in suspected syncope patients. Netherlands Trial Registration: NTR5651. Registered 29 January 2016, https://www.trialregister.nl/trial/5532.

Orthostatic blood pressure measurements are often overlooked during the initial evaluation of syncope in the emergency department.

The renewed 2018 syncope guidelines published by the European Society of Cardiology (ESC) reiterate that the initial evaluation of syncope should include history taking, physical examination, an electrocardiogram, and orthostatic blood pressure measurements (OBPM). However, the importance of evaluating for orthostatic hypotension (OH) often remains underappreciated in clinical practice. In this study, we examine the initial evaluation of syncope on an ED. We retrospectively reviewed 2 years of consecutive medical records of patients presenting with a syncope to the ED of a university hospital. We collected patient demographics and data on initial syncope evaluation for further analysis. In a cohort of 289 patients, OBPM and ECG were performed in 16 and 89% of the cases, respectively. An OBPM was performed in only 52% of the patients who received a working diagnosis of OH. In the other 48%, the OH diagnosis was likely made on the basis of history taking and exclusion of other syncope causes. OBPM are infrequently used during the initial evaluation of syncope irrespective of its consistent inclusion in ESC syncope guidelines. The discordance between clinical practice and the ESC syncope guidelines calls for increased awareness of the role of OBPM in the initial evaluation of syncope by either stricter guideline adherence or reappraisal of clinical practice.

Hemodynamic Mechanisms Underlying Initial Orthostatic Hypotension, Delayed Recovery and Orthostatic Hypotension.

OBJECTIVES: Continuous noninvasive blood pressure (BP) measurement enables us to observe rapid changes in BP and to study underlying hemodynamic mechanisms. This study aimed to gain insight into the pathophysiological mechanisms underlying short-term orthostatic BP recovery patterns in a real-world clinical setting with (pre)syncope patients. SETTING AND PARTICIPANTS: In a prospective cohort study, the active lying-to-standing test was performed in suspected (pre)syncope patients in the emergency department with continuous noninvasive finger arterial BP measurement. MEASURES: Changes in systolic BP, cardiac output (CO), and systemic vascular resistance (SVR) were studied in normal BP recovery, initial orthostatic hypotension, delayed BP recovery, and sustained orthostatic hypotension. RESULTS: In normal recovery (n = 47), ΔBP at nadir was -24 (23) mmHg, with a CO change of +10 (21%) and SVR of -23 (21%). In initial orthostatic hypotension (n = 7) ΔBP at nadir was -49 (17) mmHg and CO and SVR change was -5 (46%) and -29 (58%), respectively. Delayed recovery (n = 12) differed significantly from normal recovery 30 seconds after standing, with a ΔBP of -32 (19) vs 1 (16) mmHg, respectively. Delayed recovery was associated with a significant difference in SVR changes compared to normal recovery, -17 (26%) vs +4 (20%), respectively. There was no difference in CO changes. In sustained orthostatic hypotension (n = 16), ΔBP at 180 seconds after standing was -39 (21) mmHg, with changes in CO of -16 (31%) and SVR of -9 (20%). CONCLUSIONS/IMPLICATIONS: Hemodynamic patterns following active standing are heterogeneous and differ across orthostatic BP recovery patterns, suggesting that volume status, medication use, and autonomic dysfunction should all be taken into account when evaluating these patients. Moreover, results suggest that a delayed BP recovery is associated with an impaired increase in SVR in a significant proportion of individuals, implying that physicians treating older adults with hypertension should consider the possible negative effect of intensive hypertension treatment on initial orthostatic blood pressure control.

Orthostatic blood pressure recovery patterns in suspected syncope in the emergency department.

INTRODUCTION: Orthostasis is a frequent trigger for (pre)syncope but some forms of orthostatic (pre)syncope have a worse prognosis than others. Routine assessment of orthostatic BP in the ED can detect classic orthostatic hypotension, but often misses these other forms of orthostatic (pre)syncope. This study aimed to determine the frequency of abnormal orthostatic BP recovery patterns in patients with (pre)syncope by using continuous non-invasive BP monitoring. METHODS: We performed a prospective cohort study in suspected patients with (pre)syncope in the ED of a tertiary care teaching hospital between January and August 2014. Orthostatic BP was measured during the active lying-to-standing test with Nexfin, a continuous non-invasive finger arterial pressure measurement device. Orthostatic BP recovery patterns were defined as normal BP recovery, initial orthostatic hypotension, delayed BP recovery, classic orthostatic hypotension and reflex-mediated hypotension. RESULTS: Of 116 patients recruited, measurements in 111 patients (age 63 years, 51% male) were suitable for analysis. Classic orthostatic hypotension was the most prevalent abnormal BP pattern (19%), but only half of the patients received a final diagnosis of orthostatic hypotension. Initial orthostatic hypotension and delayed BP recovery were present in 20% of the patients with (pre)syncope of whom 45% were diagnosed as unexplained syncope. Reflex-mediated hypotension was present in 4% of the patients. CONCLUSION: Continuous non-invasive BP measurement can potentially identify more specific and concerning causes of orthostatic (pre)syncope. Correct classification is important because of different short-term and long-term clinical implications.

Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild sepsis in the emergency department: a pilot study.

OBJECTIVE: We investigated whether combining the caval index, assessment of the global contractility of the heart and measurement of stroke volume with Noninvasive Cardiac Output Monitoring (NICOM) can aid in fluid management in the emergency department (ED) in patients with sepsis. SETTING: A prospective observational single-centre pilot study in a tertiary care centre. PRIMARY AND SECONDARY OUTCOMES: Ultrasound was used to assess the caval index, heart contractility and presence of B-lines in the lungs. Cardiac output and stroke volume were monitored with NICOM. Primary outcome was increase in stroke volume after a fluid bolus of 500 mL, while secondary outcome included signs of fluid overload. RESULTS: We included 37 patients with sepsis who received fluid resuscitation of at least 500 mL saline. The population was divided into patients with a high (>36.5%, n=24) and a low caval index (<36.5%, n=13). We observed a significant increase (p=0.022) in stroke volume after 1000 mL fluid in the high caval index group in contrast to the low caval index group but not after 500 mL of fluid. We did not find a significant association between global contractility of the left ventricle and the response on fluid therapy (p=0.086). No patient showed signs of fluid overload. CONCLUSIONS: Our small pilot study suggests that at least 1000 mL saline is needed to induce a significant response in stroke volume in patients with sepsis and a high caval index. This amount seems to be safe, not leading to the development of fluid overload. Therefore, combining ultrasound and NICOM is feasible and may be valuable tools in the treatment of patients with sepsis in the ED. A larger trial is needed to confirm these results.

Effects of aging on the cerebrovascular orthostatic response.

When healthy subjects stand up, it is associated with a reduction in cerebral blood velocity and oxygenation although cerebral autoregulation would be considered to prevent a decrease in cerebral perfusion. Aging is associated with a higher incidence of falls, and in the elderly falls may occur particularly during the adaptation to postural change. This study evaluated the cerebrovascular adaptation to postural change in 15 healthy younger (YNG) vs. 15 older (OLD) subjects by recordings of the near-infrared spectroscopy-determined cerebral oxygenation (cO2Hb) and the transcranial Doppler-determined mean middle cerebral artery blood velocity (MCA V(mean)). In OLD (59 (52-65) years) vs. YNG (29 (27-33) years), the initial postural decline in mean arterial pressure (-52 ± 3% vs. -67 ± 3%), cO2Hb (-3.4 ± 2.5 µmoll(-1) vs. -5.3 ± 1.7 µmoll(-1)) and MCA V(mean) (-16 ± 4% vs. -29 ± 3%) was smaller. The decline in MCA V(mean) was related to the reduction in MAP. During prolonged orthostatic stress, the decline in MCA V(mean)and cO(2)Hb in OLD remained smaller. We conclude that with healthy aging the postural reduction in cerebral perfusion becomes less prominent.

Prospective evaluation of non-pharmacological treatment in vasovagal syncope.

AIMS: Initial treatment of vasovagal syncope (VVS) consists of assuring an adequate fluid and salt intake, regular exercise and application of physical counterpressure manoeuvres. We examined the effects of this non-pharmacological treatment in patients with frequent recurrences. METHODS AND RESULTS: One hundred patients with > or =3 episodes of VVS in the 2 years prior to the start of the study openly received non-pharmacological treatment. We evaluated this treatment both with respect to syncopal recurrences, factors associated with recurrence, and quality of life (QoL). The median number of syncopal recurrences was lower in the first year of non-pharmacological treatment compared with the last year before treatment (median 0 vs. 3; P < 0.001), but 49% of patients experienced at least one recurrence. In multivariable analysis, a higher syncope burden prior to inclusion was significantly associated with syncopal recurrence. Disease-specific QoL improved over time, with larger improvements for patients with more reduction in syncope burden. CONCLUSION: In patients with frequent recurrences of VVS, non-pharmacological treatment has a beneficial effect on both syncopal recurrence and QoL, but nearly half of these patients still experience episodes of syncope.

Central and cerebrovascular effects of leg crossing in humans with sympathetic failure.

Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure. This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between MCA Vmean (middle cerebral artery blood velocity; using transcranial Doppler ultrasound), frontal lobe oxygenation [O2Hb (oxyhaemoglobin)] and MAP (mean arterial pressure), CO (cardiac output) and TPR (total peripheral resistance) in six patients (aged 37-67 years; three women) and age- and gender-matched controls during leg crossing. In the patients, leg crossing increased MAP from 58 (42-79) to 72 (52-89) compared with 84 (70-95) to 90 (74-94) mmHg in the controls. MCA Vmean increased from 55 (38-77) to 63 (45-80) and from 56 (46-77) to 64 (46-80) cm/s respectively (P<0.05), with a larger rise in O2Hb [1.12 (0.52-3.27)] in the patients compared with the controls [0.83 (-0.11 to 2.04) micromol/l]. In the control subjects, CO increased 11% (P<0.05) with no change in TPR. By contrast, in the patients, CO increased 9% (P<0.05), but also TPR increased by 13% (P<0.05). In conclusion, leg crossing improves cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects, cerebral perfusion and oxygenation were improved by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure, cerebral perfusion and oxygenation were improved through a rise in MAP due to increments in both CO and TPR.

Reconstruction of brachial pressure from finger arterial pressure during orthostasis.

INTRODUCTION: In patients with recurrent syncope, monitoring of intra-arterial pressure during orthostatic stress testing is recommended because of the potentially sudden and rapid development of hypotension. Replacing brachial arterial pressure (BAP) by the non-invasively obtained finger arterial pressure (FinAP) has advantages because catheterization in itself may provoke a syncope. OBJECTIVE: To investigate whether reconstruction of the brachial pressure curve (ReBAP) from FinAP can account for systolic and diastolic offset in the recorded pressure on the transition from a supine to an upright position and during maintained postural stress. METHODS: In nine healthy young subjects BAP and FinAP were recorded in the supine position, during 8 min of standing and during 20 min of 70degrees passive head-up tilt (HUT70) whereafter three of the subjects fainted within 20 min of HUT. The FinAP signal was modeled off-line into a reconstructed brachial pressure curve. RESULTS: For FinAP but not for ReBAP, systolic (P < 0.05) and diastolic (P < 0.001) bias increased in the transition from the supine to the HUT position. Bias for the systolic pressure in the supine position and after 7.5 and 20 min of HUT were 2, 7 and 11 mmHg for FinAP but only 0, -2 and 1 mmHg for ReBAP (P < 0.05 for HUT). For the diastolic pressure these values were -2, 5 and 8 mmHg for FinAP and 4, 5 and 6 for ReBAP (P < 0.01 for supine). CONCLUSIONS: Brachial pressure reconstruction from the finger arterial pressure waveform accounts for the bias from the supine to the upright position, eliminates the bias for the systolic but not for diastolic finger pressure and reduces the trend in diastolic bias with increased tilt duration.

Postural effects on cardiac output and mixed venous oxygen saturation in humans.

The activation of cardiovascular reflexes for postural adaptation questions whether, in healthy humans, the central blood volume is optimised to support the upright position. A functional definition of an 'optimal circulating volume' that provides the heart with enough central blood volume to establish a maximal cardiac output (CO) and mixed venous oxygen saturation (S(v,O2)) at rest was evaluated in nine healthy subjects. Preload to the heart was varied by passively changing the body position from 70 deg head-up to 20 deg head-down tilt. The S(v,O2) was compared with simultaneously measured estimates of CO by computer-controlled thermodilution. The CO was in the range 8.7-3.8 l min(-1) and S(v,O2) was in the range 79-58 %. Neither CO (median 6.0 (range 5.3-8.7) l min(-1)) nor S(v,O2) (mean +/- S.D. 73.6 +/- 2.6 %) changed from the supine to the 20 deg head-down position. During sustained 70 deg head-up tilt, S(v,O2) decreased to 64 +/- 4 % together with a decline in CO to 4.7 (3.9-5.6) l min(-1) (P < 0.05). Under conditions of varying tilt angles, a change in CO is paralleled by concordant changes in S(v,O2). Maximal values for CO and S(v,O2) during supine rest suggest that the horizontal position provides for an 'optimal' central blood volume.