PurposeThe heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior... Show morePurposeThe heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior cervical ganglia (SCG) is used in many experimental studies. The clinical relevance of the SCG to cardiac innervation is controversial. We investigated current morphological and functional evidence as well as controversies on the contribution of the SCG to cardiac innervation.MethodsA systematic literature review was conducted in PubMed, Embase, Web of Science, and COCHRANE Library. Included studies received a full/text review and quality appraisal.ResultsSeventy-six eligible studies performed between 1976 and 2023 were identified. In all species studied, morphological evidence of direct or indirect SCG contribution to cardiac innervation was found, but its contribution was limited. Morphologically, SCG sidedness may be relevant. There is indirect functional evidence that the SCG contributes to cardiac innervation as shown by its involvement in sympathetic overdrive reactions in cardiac disease states. A direct functional contribution was not found. Functional data on SCG sidedness was largely unavailable. Information about sex differences and pre- and postnatal differences was lacking.ConclusionCurrent literature mainly supports an indirect involvement of the SCG in cardiac innervation, via other structures and plexuses or via sympathetic overdrive in response to cardiac diseases. Morphological evidence of a direct involvement was found, but its contribution seems limited. The relevance of SCG sidedness, sex, and developmental stage in health and disease remains unclear and warrants further exploration.Graphical abstractAn overview of the current literature derived from morphological and functional data on the involvement of SCG in cardiac innervation, relevance of sidedness, sex differences, and pre- and postnatal differences in various species. X = Information not available Show less
Rossum, I.A. van; Lange, F.J. de; Benditt, D.G.; Zwet, E.W. van; Houwelingen, M. van; Thijs, R.D.; Dijk, J.G. van 2023
PurposeWe compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope.MethodsThe study included subjects with a decrease in... Show morePurposeWe compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope.MethodsThe study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition.ResultsA total of 149 subjects with a median age of 43 (interquartile range 24–60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition.ConclusionSubjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition. Show less
PurposeTo understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe.MethodsWe invited 84 European autonomic centers to... Show morePurposeTo understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe.MethodsWe invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders.ResultsForty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN–EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020–2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year.ConclusionsThe COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design. Show less
An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when... Show moreAn expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres. Show less
Ghariq, M.; Thijs, R.D.; Bek, L.M.; Zwet, E.W. van; Benditt, D.G.; Dijk, J.G. van 2020
Purpose Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods We retrospectively studied TTT outcomes in suspected... Show morePurpose Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods We retrospectively studied TTT outcomes in suspected VVS. TTT consisted of supine rest, a maximum 20 min of head-up tilt without and, if nitroglycerin was needed, a further maximum 20 min after nitroglycerin administration. TTT was terminated if VVS occurred. We used binary logistic regression for the entire TTT and for each phase, with VVS as outcome and age and sex as predictors. Results TTT provoked vasovagal (pre)syncope in 494 out of 766 tests (64%). The proportion of men and women who fainted during the entire TTT did not differ significantly between the sexes (p = 0.13, corrected for age). A lower proportion of women than men had VVS in the phase without nitroglycerin (odds ratio 0.54; 95% confidence interval 0.37-0.79;p = 0.002, corrected for age), whereas a higher proportion of women than men fainted after nitroglycerin (odds ratio 1.58; 95% confidence interval 1.13-2.21;p = 0.008, corrected for age). These sex differences remained significant after correction for a history of orthostatic versus emotional triggers. The effect of sex on TTT outcome was closely associated with differences of blood pressure change upon tilt-up (lower in men in both TTT phases: without nitroglycerinp = 0.003; with nitroglycerinp = 0.05), but not with heart rate changes. Conclusion Men were more susceptible to induction of VVS without nitroglycerin and women after it. The unexpected findings may be due to sex-specific pathophysiological differences. Show less
Bel, R. van der; Verbree, J.; Gurney-Champion, O.J.; Osch, M.J.P. van; Stroes, E.S.G.; Nederveen, A.J.; Krediet, C.T.P. 2020
Purpose There is ample evidence that systemic sympathetic neural activity contributes to the progression of chronic kidney disease, possibly by limiting renal blood flow and thereby inducing renal... Show morePurpose There is ample evidence that systemic sympathetic neural activity contributes to the progression of chronic kidney disease, possibly by limiting renal blood flow and thereby inducing renal hypoxia. Up to now there have been no direct observations of this mechanism in humans. We studied the effects of systemic sympathetic activation elicited by a lower body negative pressure (LBNP) on renal blood flow (RBF) and renal oxygenation in healthy humans. Methods Eight healthy volunteers (age 19-31 years) were subjected to progressive LBNP at - 15 and - 30 mmHg, 15 min per level. Brachial artery blood pressure was monitored intermittently. RBF was measured by phase-contrast MRI in the proximal renal artery. Renal vascular resistance was calculated as the MAP divided by the RBF. Renal oxygenation (R2*) was measured for the cortex and medulla by blood oxygen level dependent (BOLD) MRI, using a monoexponential fit. Results With a LBNP of - 30 mmHg, pulse pressure decreased from 50 +/- 10 to 43 +/- 7 mmHg; MAP did not change. RBF decreased from 1152 +/- 80 to 1038 +/- 83 mL/min to 950 +/- 67 mL/min at - 30 mmHg LBNP (p = 0.013). Heart rate and renal vascular resistance increased by 38 +/- 15% and 23 +/- 8% (p = 0.04) at - 30 mmHg LBNP, respectively. There was no change in cortical or medullary R2* (20.3 +/- 1.2 s(-1) vs 19.8 +/- 0.43 s(-1); 28.6 +/- 1.1 s(-1) vs 28.0 +/- 1.3 s(-1)). Conclusion The results suggest that an increase in sympathetic vasoconstrictor drive decreases kidney perfusion without a parallel reduction in oxygenation in healthy humans. This in turn indicates that sympathetic activation suppresses renal oxygen demand and supply equally, thus allowing adequate tissue oxygenation to be maintained. Show less
In autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are... Show moreIn autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are contradictory. We evaluated pooling using strain-gauge plethysmography (SGP) during head-up tilt (HUT) with a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs and thus to maximise pooling. 23 healthy subjects and 12 patients with AF were tilted for 5 min. BP and calf volume changes, as measured by SGP, were measured continuously. Multiple regression analysis was used to examine the effect of AF on orthostatic fluid shifts after adjustment for potential confounders. Patients did not differ from controls with respect to the increase of calf volume after 5 min HUT. The acute (0-1 min) and the prolonged (1-5 min) phases of calf volume responses to HUT were also similar between patients and controls. No correlation was found between the degree of orthostatic hypotension and the orthostatic calf volume change in AF. In one patient an additional measurement was made before rising from bed in the early morning demonstrating a greater albeit small increase of calf volume upon HUT. Orthostatic fluid shifts at the level of the calf in AF are not augmented during the course of the day despite marked hypotension. However, a small increase of pooling may be expected when the patient first gets out of bed in the morning probably due to the absence of oedema. Show less
