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Influence of Age on Magnitude and Timing of Vasodepression and Cardioinhibition in Tilt-Induced Vasovagal Syncope
Abstract
Background
Cardioinhibition may diminish with age, but the changing balance of cardioinhibition and vasodepression with age has not been quantified, leaving the mechanism of vasovagal syncope (VVS) in old age unclear.
Objectives
This study sought to quantify age-related changes of vasodepression and cardioinhibition in tilt-induced VVS.
Methods
We studied 163 cases of tilt-induced VVS, evoked using the Italian protocol with blood pressure, heart rate, and video-electroencephalographic monitoring. Presyncope was excluded. Cardioinhibition was defined as the heart rate decrease before syncope; asystolic pauses (≥3 seconds) were divided into early and late asystole, ie, beginning early enough to or too late to be the major cause of loss of consciousness. The log-ratio method was used to quantify contributions of cardioinhibition and vasodepression, assessed in 2 10-second periods before the onset of cardioinhibition and before syncope.
Results
With increasing age, cardioinhibition decreased, ie, heart rate decreased less and more slowly near syncope (P < 0.0001), while vasodepression increased. Asystolic pauses were less frequent in the older one-half of the group than the younger one-half (26% vs 57%; P < 0.00001), but when it did, late asystole occurred more often (58% vs 15%; P < 0.001).
Conclusions
The shift toward less cardioinhibition and more vasodepression with increased age probably reflects a physiological shift in circulatory control. The weakening of cardioinhibition with age may detract from the efficacy of pacing in older patients with VVS. Cardioinhibition-vasodepression balance should be considered in pacing decisions in older subjects with VVS.
... The sensitivity percentage of the test in the elderly may be similar to non-elderly patients with a protocol using sublingual nitroglycerin, with positivity in the active phase being higher in the elderly, especially those over 75 years of age [12][13][14] . ...
... In this context, elderly people without a described and established diagnosis presenting recurrent falls may suffer from high morbidity. 12,14 . ...
... Considering that 23.06% of the elderly presented a vasovagal response, 5, 22% showed a dysautonomic reaction. Cardioinhibitory responses may be less frequent in the elderly, although we did not find significant differences due to the low number in this group 14 . ...
Introduction: The elderly have several causes of syncope or pre-syncope. The importance of the Tilt Test (TT) has been questioned in this population. However, dysautonomic causes are common in these age groups, having an impact on morbidity and mortality. Objective: Compare the results of the TT between the age groups of the elderly (>=60 years) and the non-elderly. Methods: Crosssectional study carried out between 2016-2021. We used the Mann-Whitney and Chi-square tests, with a p-value < 5% considered significant. The protocols used were Westminster or Italian. Results: We analyzed 2364 tilt tests, 61.7% female, aged 51.1 (31-71) years. Positivity was 32.6%, 37.2% with sensitization (p < 0.0001). In the elderly group (EG), there were 958 tests (40.5%) and 1381 (58.4%) in the non-elderly (NEG). EG positivity was 270 (28.0%), lower than NEG with 524 (37.43%) (p < 0.01). Positivity with sensitization in EG was 195 (20.35%) x 403(29.18%) in NEG (p<0.001). In EG, 50 patients (5.22%) had a dysautonomic response and in NEG, there were 10 (0.72%) (p < 0.001). Complications were 4.2% EG x 2.6% NEG ( p= 0.03). Conclusion: The TT in the elderly showed a lower incidence of positivity in the passive and sensitization phases compared to the non-elderly. Vasovagal causes were the most frequent causes in the elderly, had a higher incidence of dysautonomic responses, fewer prodromes and a higher rate of complications, however without severity.
... In fact, asystole during tilt-evoked VVS started after patients had already lost consciousness in about one-third of cases. 7 As such 'late asystole' occurred more often in older than in younger patients with VVS, 8 preventing syncope by preventing asystole was most likely successful in younger patients in whom pacing was contra-indicated anyway. In summary, attempts aimed at the prevention of extreme bradycardia only through pacing had a considerable chance of failure. ...
... The realization that CI had a profound effect on BP over the entire CI duration suggested that keeping HR at a high corrective level would slow the BP decrease and give patients time to prevent syncope, e.g. by sitting down. 5,8,9 It seems that CLS pacing does just that: Russo et al. reported that CLS pacing started when HR was around 88 bpm, after which HR increased to 105 bpm and later to 95 bpm. Pacing started at a median of 1.7 min before syncope, which supports the idea that CLS prevented CI altogether: in the earlier-mentioned VVS study, 5 CI started a median of 58 s before syncope. ...
... Blood pressure kept decreasing due to a continuing fall of SV (venous vasodepression) and a moderate decrease of TPR (arterial vasodepression). 5,8 This continuing decrease of BP was noticeably also present in the study by Russo et al., in which syncope eventually occurred in most patients. ...
... The relative contributions of VD and CI in VVS vary among subjects [9]. Results from tilt table test (TTT) studies have suggested a higher incidence of asystole in younger subjects [19,20,28], although in some studies this finding may have been biased by early termination of the procedure by tilting back in older subjects [4,16,19,22]. The modified VAsovagal Syncope International Study (VASIS) criteria defined CI as a HR < 40/min for at least 10 s or asystole > 3 s. ...
... In addition, 42% of our subjects had an asystolic pause in HR ≥ 3 s, which is higher than the 6-32% described in the literature [4]. Our high rate of pause in HR is probably due to our strict inclusion criteria, with only subjects with complete syncope documented with video EEG, as the occurrence of CI and asystole during a TTT strongly depends on decisions when to tilt back [20,28]. ...
... The final increase in HR in the strong CI subgroup can be seen as a last-ditch physiological attempt to increase BP. This HR increase in the strong CI subgroup, which contained younger subjects, is in line with the previous finding that BP regulation depends stronger on HR in the young and more on TPR in the elderly [28]. ...
Purpose
We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope.
Methods
The 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.
Results
A 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.
Conclusion
Subjects 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.
... In the case of the need to establish a certain, highly likely or possible diagnosis after initial evaluation (Brignole et al., 2018a), staff members must be aware that the tilt must be pursued to complete loss of consciousness so that asystole and its exact timing can be revealed, if present (van Dijk et al., 2022;Saal et al., 2017). This requires some steely nerves at first and not being compliant with patient's wishes to stop before a full test including syncope is achieved (Russo, Parente, Rago, et al., 2022). ...
... Video recording with EEG is important to exclude epilepsy when the event is accompanied by muscle jerks or strong motor phenomena. A normal EEG during a recognized event on TTT excludes epilepsy that presents as TLOC, that is, tonic, clonic and tonic-clonic seizures (van Dijk et al., 2009). When TTT is negative for an event, this does not exclude PPS, then catching an event by the camera (e.g., on smartphone) by an eyewitness should be the next step to confirm the diagnosis of PPS. ...
... The 'Italian protocol' for tilt (Bartoletti et al., 2000), which is the most widely applied, allows more than 20 min by administering sublingual NTG 300-400 mcg at 20 min of tilt, as mentioned before. VVS commences its collapse with HR fall (cardioinhibition) which occurs relatively rapidly compared with the slow development of BP fall over the preceding ∼8 min (van Dijk et al., 2020(van Dijk et al., , 2022. ...
Tilt table testing (TTT) has been used for decades to study short‐term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence‐based practice syncope guidelines, proper application and interpretation of TTT in the day‐to‐day care of syncope patients remain challenging. In this review, we offer practical information on what is needed to perform TTT, how results should be interpreted including the Vasovagal Syncope International Study classification, why syncope induction on TTT is necessary in patients with unexplained syncope and on indications for TTT in syncope patient care. The minimum requirements to perform TTT are a tilt table with an appropriate tilt‐down time, a continuous beat‐to‐beat BP monitor with at least three electrocardiogram leads and trained staff. We emphasize that TTT remains a valuable asset that adds to history building but cannot replace it, and highlight the importance of recognition when TTT is abnormal even without syncope. Acknowledgement by the patient/eyewitness of the reproducibility of the induced attack is mandatory in concluding a diagnosis. TTT may be indicated when the initial syncope evaluation does not yield a certain, highly likely, or possible diagnosis, but raises clinical suspicion of (1) reflex syncope, (2) orthostatic hypotension (OH), (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT in the patient with a certain, highly likely or possible diagnosis of reflex syncope, may be to educate patients on prodromes. In patients with reflex syncope with OH TTT can be therapeutic to recognize hypotensive symptoms causing near‐syncope to perform physical countermanoeuvres for syncope prevention (biofeedback). Detection of hypotensive susceptibility requiring therapy is of special value.
... While peripheral resistance was not impacted by cardioinhibition, the reduction in the stroke volume negatively impacted BP and produced an ineffective corrective increase in HR, which was unable to compensate for the decline in BP [78]. In a subsequent study, the authors highlighted that aging had a significative impact on cardioinhibition and vasodilation, as it was associated with a diminished increase in HR and a faster BP decline [79]. Therefore, the authors questioned the utility of pacing in older patients with vasovagal syncope. ...
... For example, bradycardia is the most common cause of cardiac syncope, and it is treated with PM implantation. Nevertheless, the coexistence of hypotension reduces pacing efficacy [79,88]. On the other hand, the management of reflex or orthostatic syncope is more complex since specific therapies are less effective [89]. ...
Syncope is a highly prevalent clinical condition characterized by a rapid, complete, and brief loss of consciousness, followed by full recovery caused by cerebral hypoperfusion. This symptom carries significance, as its potential underlying causes may involve the heart, blood pressure, or brain, leading to a spectrum of consequences, from sudden death to compromised quality of life. Various factors contribute to syncope, and adhering to a precise diagnostic pathway can enhance diagnostic accuracy and treatment effectiveness. A standardized initial assessment, risk stratification, and appropriate test identification facilitate determining the underlying cause in the majority of cases. New technologies, including artificial intelligence and smart devices, may have the potential to reshape syncope management into a proactive, personalized, and data-centric model, ultimately enhancing patient outcomes and quality of life. This review addresses key aspects of syncope management, including pathogenesis, current diagnostic testing options, treatments, and considerations in the geriatric population.
... The two main components of VVS include vasodepression and cardioinhibition [1]. While a cardioinhibitory response is often seen in younger individuals, the vasodepressor component is more prevalent in older ages [25,26]. In patients with VVS, the initial vasodepressive phase results in sympathetic withdrawal and causes blood pooling in the abdomen and lower limbs that contributes to the reduction in venous return [27]. ...
Purpose of Review
Cardioneuroablation (CNA) has emerged as a potential alternative to pacemaker therapy in well-selected cases with vasovagal syncope (VVS). In recent years, the number of CNA procedures performed by electrophysiologists has considerably risen. However, some important questions, including proper patient selection and long-term results, remain unanswered. The present article aims to critically review and interpret latest scientific evidence for clinical indications and how to approach long-term management.
Recent Findings
CNA is a new approach that has been supported mainly by retrospective or observational data for its use in syncope. Overall, in mixed population studies treated with CNA, 83.3 to 100% have been reported to be free of syncope over follow-up periods of 6 to 52.1 months. For studies including patients who underwent CNA with pure VVS, 73.2 to 100% have been reported to be syncope-free over follow-up periods of 4 to 45.1 months. One large meta-analysis showed 91.9% freedom from syncope after CAN. To date, only one randomized controlled trial with small case number has been performed of CNA compared to non-pharmacological treatment in VVS. In this study of 48 patients with an average of 10 ± 9 spontaneous syncopal episodes prior to study enrollment and 3 ± 2 episodes in the year prior to CNA. After CNA, 92% were free of syncope compared with 46% treated with optimal non-pharmacological treatment to prevent new syncope episodes (P = 0.0004). To date, most studies have included younger patients (< 60 years of age). There are only limited data in patients older than 60, and some studies suggest less of an effect in relatively older patients.
Summary
Cardioneuroablation can be performed to decrease syncope recurrence in adult patients aged < 60 years, with severe or recurrent cardioinhibitory syncope without prodromal symptoms, after proven failure of conventional therapies. Due to a paucity of data supporting efficacy in older individuals or for vasodepressor components, CNA in adult patients aged > 60 years or in the presence of a dominant vasodepressor should be considered investigational in severely symptomatic patients after proven failure of pharmacological and non-pharmacological therapies.
... The main haemodynamic mechanisms of reflex syncope include cardioinhibition and vasodepression. 3 Cardioinhibition typically predominates in younger individuals, while vasodepression is stronger at old age 21,24 (Figure 2). Cardioinhibition is due to marked activation of the vagal nerve, while vasodepression is largely due to a transient inhibition of the sympathetic system. ...
Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.
... 2. Cardioinhibition, i.e. a vagal heart rate fall due to sinus slowing that may include asystole of usually < 20 s. Cardioinhibition decreases with age [14] but is very common in childhood. Asystole is probably ubiquitous in VVS in toddlers. ...
This paper aims to improve the diagnosis of syncope and transient loss of consciousness (TLOC) in children. Diagnostic problems stem, first, from some causes spanning various disciplines, e.g. cardiology, neurology and psychiatry, while the most common cause, vasovagal syncope, is not embraced by any specialty. Second, clinical variability is huge with overlapping signs and symptoms. Third, the approach to TLOC/syncope of the European Society of Cardiology (ESC) is underused in childcare. We explain the ESC guidelines using an additional paediatric literature review. Classification of TLOC and syncope is hierarchic and based on history taking. Loss of consciousness (LOC) is defined using three features: abnormal motor control including falling, reduced responsiveness and amnesia. Adding a < 5 min duration and spontaneous recovery defines TLOC. TLOC simplifies diagnosis by excluding long LOC (e.g. some trauma, intoxications and hypoglycaemia) and focussing on syncope, tonic–clonic seizures and functional TLOC. Syncope, i.e. TLOC due to cerebral hypoperfusion, is divided into reflex syncope (mostly vasovagal), orthostatic hypotension (mostly initial orthostatic hypotension in adolescents) and cardiac syncope (arrhythmias and structural cardiac disorders). The initial investigation comprises history taking, physical examination and ECG; the value of orthostatic blood pressure measurement is unproven in children but probably low. When this fails to yield a diagnosis, cardiac risk factors are assessed; important clues are supine syncope, syncope during exercise, early death in relatives and ECG abnormalities.
Conclusions: In adults, the application of the ESC guidelines reduced the number of absent diagnoses and costs; we hope this also holds for children.What is Known:
• Syncope and its mimics are very common in childhood, as they are at other ages.
• Syncope and its mimics provide considerable diagnostic challenges.
What is New:
• Application of the hierarchic framework of transient loss of consciousness (TLOC) simplifies diagnosis.
• The framework stresses history-taking to diagnose common conditions while keeping an eye on cardiac danger signs.
... This concept is not supported by the lack of data from tilt-testing showing dominant VD (VASIS type 3), 18 it appears to be rare and, also not supported by recent reports of VVS pathophysiology. 12,13 Efficacy has been clinically shown with both sensors 4-6 but comparative efficacy has never been evaluated. Functionally, the CLS sensor appears more physiologically based on its earlier intervention in the evolution of VVS. 15 This possible superiority of CLS over RDR based on its earlier intervention requires demonstration in the interest of optimal patient care. ...
Background:
Pacing for vasovagal syncope is established. Two pacing algorithms are available. The rate-drop-response (RDR-Medtronic) is triggered by falling heart rate acting with modified rate-hysteresis. The closed loop stimulation or system (CLS-Biotronik) is triggered by impedance changes in the right ventricle reflecting falling volume and rising contractility. These are very different physiologically. Both algorithms carry favorable reports in clinical use.
Methods:
A randomized-controlled superiority trial is proposed to compare the two algorithms for the control of vasovagal syncope in patients for whom pacing is indicated by current guidelines in North America and Europe. Available recent evidence may be seen as supporting superiority of CLS. No comparison between the two algorithms has been made. In this trial, patients will be centrally randomized to one or other algorithm on a 1:1 basis. Two-hundred-seventy-six patients in each group will be recruited. Sample size is determined using a confidence interval of 95%, a power of 90%, and a drop-out rate of 10% to detect an 11% difference between CLS and RDR. Recurrent symptom comparison will be made by an independent committee. The Co-primary endpoints will be recurrent syncope burden compared with that in 24-months preimplant, and occurrence of syncope in 24-months follow-up. Each outcome will be compared between the two algorithms. Secondary endpoints will be program and drug therapy changes over 24-months follow-up and quality of life by questionnaire at baseline,1 and 2 years.
Results and conclusions:
These are anticipated to clarify the device algorithm choice and, therefore, to improve patient care.
... A positions sensor on the implantable loop recorders may help to distinct hypotension not related to cardioinhibition. When a patient experiences a syncope fall, the position sensor helps confirm the vaso-depressive reflex episodes or even, more specifically, helps identify the significant cardio-inhibition occurring after a fall (late asystole), suggesting that pacing is unlikely to help [21]. Furthermore, the implantable loop recorder approach is much more expensive. ...
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.
... In the context of CI reflex, it is important to mention the role of age. As demonstrated by several independent studies, while vagal cardiac overactivity and sinus depression dominate in younger patients, vasodepression is more prevalent in older age, beginning with the age of 50 years [16,17]. ...
Introduction:
Treatment efficacy of reflex syncope is mainly related to the mechanism underlying syncope rather than its etiology or clinical presentation. The predominant mechanism underlying reflex syncope can be assigned to hypotensive or to bradycardic phenotypes.
Areas covered:
Methodology and diagnostic criteria of the most useful tests for the identification of hypotensive and bradycardic phenotypes are discussed. Diagnostic tests for the hypotensive phenotype include office blood pressure measurement with active standing test, home, and wearable blood pressure monitoring, 24-h ambulatory blood pressure monitoring and tilt table test. Diagnostic tests for the bradycardic phenotype include carotid sinus massage, tilt table test and prolonged ECG monitoring.
Expert opinion:
In reflex syncope, the documentation of bradycardia/asystole during a syncopal episode does not rule out the possibility that a preceding or parallel hypotensive reflex plays an important role. Similarly, even when a hypotensive mechanism is established, the possibility of an associated cardioinhibitory reflex should be investigated. Investigating the mechanism of reflex syncope is mandatory in patients with severe recurrent episodes, with the final aim to develop a personalized treatment strategy. Recent trials have demonstrated the benefits of personalized mechanism-based therapy, thus highlighting the importance of a comprehensive assessment of the mechanisms underlying syncope.
Increased vagal activity plays a prominent role in vasovagal syncope (VVS). The aim of this study was to characterize vagal function in VVS by evaluating the heart rate (HR) deceleration capacity (DC) and the HR deceleration runs (DRs) in patients with VVS between attacks.
A total of 188 consecutive VVS patients were enrolled in the study, of whom 129 had positive head-up tilt test (HUTT); 132 healthy participants were enrolled as controls. DC, DRs (DR2, i.e., episodes of 2 consecutive beat-to-beat HR decelerations), and the sum of DR8-10 (very long DR [VLDR]) were calculated using 24-h electrograms. Clinical characteristics, DC, and DRs were compared among syncope groups and controls.
Patients with VVS had higher DC (10.63 ± 2.1 vs. 6.58 ± 1.7 ms; P < 0.001) and lower minimum HR and DR6-10 than controls. No significant differences in DC or DR6-10 were found between the patients with positive and those with negative HUTT results. In multivariate logistic regression analysis, minimum HR ≥ 40 bpm (odds ratio [OR] 0.408, 95% confidence interval [CI] 0.167–0.989; P = 0.048), daytime DC ≥ 7.37 ms (OR 3.040, 95% CI 1.220–7.576; P = 0.013), and VLDR ≥ 0.046% (OR 0.306, 95% CI 0.138–0.679; P = 0.004) were demonstrated to be risk factors significantly associated with VVS.
Compared to healthy controls, patients with VVS demonstrated distinct HR deceleration profiles between attacks, including overall higher DC and lower DR6-10.
Objective:
Vasovagal syncope (VVS) is the commonest form of syncope, and malignant VVS draws substantial attention due to its life-threatening cardiac asystolic risk. This study aimed to explore the predictive role of a wide panel of clinical indicators for malignant VVS in children, and further to develop a nomogram model.
Methods:
This is a retrospective case-control study. VVS is diagnosed based on head-up tilt test (HUTT). STATA software (version 14.0) was used for statistical analysis, and effect sizes are expressed as odds ratio (OR) and 95% confidence interval (CI).
Results:
Total 370 children with VVS were analyzed, and of them 16 children had malignant VVS. Sixteen malignant VVS and 64 non-malignant VVS were matched on age and sex by a 1:4 propensity scores matching method. Mean corpuscular hemoglobin (MCH) and standard deviation of average RR intervals milliseconds (SDANN) were significantly and independently associated with malignant VVS after adjusting for confounders, with OR reaching 1.437 (95% CI: 1.044 to 1.979; P = 0.026) and 1.035 (95% CI: 1.003 to 1.068; P = 0.029), respectively. Calibration and discrimination analyses revealed that the addition of MCH and SDANN can enhance model performance. Then, a nomogram to predict malignant VVS was developed using general characteristics and two above significant factors, and higher values in medical history, number of syncope, MCH and SDANN were associated with a greater risk of malignant VVS.
Conclusion:
MCH and SDANN were two promising factors for the development of malignant VVS, and modeling of significant factors in a nomogram can provide strong reference to aid clinical decision-making.
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Flow of data from study populations to final analysis. The figure was created with BioRender.com.
The cardiac pacemaker ignites and coordinates the contraction of the whole heart, uninterruptedly, throughout our entire life. Pacemaker rate is constantly tuned by the autonomous nervous system to maintain body homeostasis. Sympathetic and parasympathetic terminals act over the pacemaker cells as the accelerator and the brake pedals, increasing or reducing the firing rate of pacemaker cells to match physiological demands. Despite the remarkable reliability of this tissue, the pacemaker is not exempt from the detrimental effects of aging. Mammals experience a natural and continuous decrease in the pacemaker rate throughout the entire lifespan. Why the pacemaker rhythm slows with age is poorly understood. Neural control of the pacemaker is remodeled from birth to adulthood, with strong evidence of age-related dysfunction that leads to a downshift of the pacemaker. Such evidence includes remodeling of pacemaker tissue architecture, alterations in the innervation, changes in the sympathetic acceleration and the parasympathetic deceleration, and alterations in the responsiveness of pacemaker cells to adrenergic and cholinergic modulation. In this review, we revisit the main evidence on the neural control of the pacemaker at the tissue and cellular level and the effects of aging on shaping this neural control.
Objective
To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT).
Methods
Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, “convex,” or decelerated, “concave”; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations.
Results
We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19–98 sec) than in VVS (median 1571 sec, IQR 1381–1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%.
Interpretation
These new hemodynamic criteria reliably differentiate cOH from VVS.
Wearable sensors to continuously measure blood pressure and derived cardiovascular variables have the potential to revolutionize patient monitoring. Current wearable methods analyzing time components (e.g., pulse transit time) still lack clinical accuracy, whereas existing technologies for direct blood pressure measurement are too bulky. Here we present an innovative art of continuous noninvasive hemodynamic monitoring (CNAP2GO). It directly measures blood pressure by using a volume control technique and could be used for small wearable sensors integrated in a finger-ring. As a software prototype, CNAP2GO showed excellent blood pressure measurement performance in comparison with invasive reference measurements in 46 patients having surgery. The resulting pulsatile blood pressure signal carries information to derive cardiac output and other hemodynamic variables. We show that CNAP2GO can self-calibrate and be miniaturized for wearable approaches. CNAP2GO potentially constitutes the breakthrough for wearable sensors for blood pressure and flow monitoring in both ambulatory and in-hospital clinical settings.
Aim
The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial.
Methods and results
We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%).
Conclusion
In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing.
Study registration
ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546.
The role of pacing in vasovagal syncope (VVS) is considered from a physiological basis. Most VVS patients lose consciousness due to hypotension before severe bradycardia/asystole occurs. Patients that benefit from dual-chamber pacing are typically older with highly symptomatic, late-onset, frequent and severe syncope with short/no prodrome and documented severe cardioinhibition. Tilt-testing is of value in patients with recurrent unexplained syncope to identify important hypotensive susceptibility stemming from reduced venous return and stroke volume. A negative tilt-test in vasovagal patients with spontaneous asystole documented by implantable/insertable loop-recorder is associated with lower syncope recurrence rates after pacemaker implantation. Pacing may be more effective if triggered by sensor detection of a parameter changing earlier in the reflex than bradycardia when stroke volume may still be relatively preserved. In this regard, detection of right ventricular impedance offers promise. In conclusion, conservatism is recommended limiting pacing in VVS to a small subset of symptomatic older patients with clearly documented cardioinhibition paying particular attention to the timing of loss of consciousness in relation to asystole/bradycardia. Understanding VVS physiology permits application of well-timed and appropriate pacing that yields benefit for highly symptomatic patients.
Aims
It is unknown how the return to supine position influences duration of loss of consciousness (LOC) and cardioinhibition during tilt test.
Methods and results
Retrospective analysis of two datasets containing records of patients who underwent tilt testing for unexplained syncope in two centres was performed. Patients, totalling 1232, were included in the study: 262 in a Swedish centre and 970 patients in a Polish centre. In Sweden, tilt table with tilt-down time (TDT) of 18 s was used (Group II). In Poland, two different tilt tables were used, one of them with TDT of 10 s (Group I, n = 325), and the other with TDT of 47 s (Group III, n = 645). Cardioinhibitory reflex occurred most frequently in Group III, whereas number of pauses >3 s, frequency of very long asystole ≥30 s, and the total duration of pauses >3 s demonstrated a trend to increase from Group I to III. Duration of LOC in Groups II and III was significantly longer compared with Group I (32.0 and 33.7 s vs. 16.4 s). In the multivariate-adjusted regression model, cardioinhibitory reflex was predicted by tilt-table model (odds ratio per model with increasing TDT: 1.40; 95% confidence interval, 1.19–1.64; P < 0.0001), whereas LOC duration was longer with increasing TDT (P < 0.0001) and age (P < 0.0001).
Conclusion
Longer TDT during induced vasovagal syncope increases the prevalence of cardioinhibitory reflex and prolongs the duration of LOC. Tilt-down time does not affect asystolic pause duration but delay may lead to occurrence of multiple pauses, higher frequency of very long asystole, and longer total asystole duration.
Syncope is defined as transient loss of consciousness as a result of cerebral hypoperfusion. Electroencephalography during syncope shows either a 'slow-flat-slow' or a 'slow' pattern. The first is believed to denote more severe hypoperfusion. Although the diagnosis of vasovagal syncope relies primarily on history taking, there is limited evidence regarding the relative importance of various clinical features, and none that relate them to the severity of electroencephalographic changes. The aim of this investigation was to study symptoms, signs and electroencephalographic changes with a 1 s resolution using electroencephalography and video data in 69 cases of tilt-induced vasovagal syncope. The main finding was that flattening of the electroencephalograph indicated more profound circulatory changes: the 'slow-flat-slow' group had a lower minimum blood pressure, longer maximum RR-interval, contained more cases with asystole and had a longer duration of loss of consciousness than the 'slow' group. Second, we describe a range of signs, including some that have rarely been reported in syncope, e.g. oral automatisms. Third, signs occurred at different rates depending on electroencephalographic flattening, suggesting a classification of syncopal signs. Type A signs (e.g. loss of consciousness, eye opening and general stiffening) develop during the first slow phase, stay present during flattening and stop in the second slow phase. Type B (particularly myoclonic jerks) occur when the electroencephalograph is slow but not flat: their abolition with electroencephalographic flattening suggests dependence on cortical activity. Type C signs (making sounds, roving eye movements and stertorous breathing) occur only in the flat phase, whereas type D (dropping the jaw and snoring) may occur either in slow or flat phases. In conclusion, our findings provide a detailed assessment of clinical symptoms in relation to electroencephalographic (EEG) changes during tilt-induced syncope.
Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated (vasovagal) syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt –induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally-mediated syncope.
Age has been identified as an independent risk factor for cardiovascular diseases. In addition, autonomic imbalance toward sympathetic preponderance has been shown to facilitate the occurrence of heart disease. Here, we aimed to assess autonomic modulation of cardiovascular parameters during normal ageing applying well-established linear and novel nonlinear parameters.
Linear and nonlinear measures of heart rate variability and complexity as well as measures of QT interval variability and baroreflex sensitivity were obtained from a total of 131 healthy, medication-free participants from a continuous age range between 20 and 90 years, who were allocated to three different age groups.
Heart rate variability and complexity significantly decreased with age, while regularity of heart rate time series increased. In addition, QT interval variability linearly increased with age, while baroreflex sensitivity showed a pronounced decrease. Overall, concerning effects of ageing, linear and nonlinear parameters showed equal differentiation between groups.
These data indicate a shift of autonomic balance toward sympathetic predominance in higher age groups, limiting the reactiveness of the cardiovascular system to adjust to different demands and increasing the risk for developing tachyarrhythmias.
Detailed history taking is of paramount importance to establish a reliable diagnosis in patients with transient loss of consciousness. In this article the clinical symptoms and signs of the successive phases of a syncopal episode are reviewed. A failure of the systemic circulation to perfuse the brain sufficiently results in a stereotyped progression of neurological symptoms and signs culminating in loss of consciousness; when transient, this is syncope. Prior to loss of consciousness the affected individual tends to exhibit unclear thinking, followed by fixation of the eyes in the midline and a 'frozen' appearance. Narrowing of the field of vision with loss of colour vision ('greying' out) and finally a complete loss of vision (hence 'blacking' out) occurs. Hearing loss may occur following loss of vision. This process may take as little as approximately 7 s in cases of sudden complete circulatory arrest (e.g. abrupt asystole), but in other circumstances it may take longer depending on the rate and depth of cerebral hypoperfusion. Complete loss of consciousness occurs with the 'turning up' of the eyeballs. Profound cerebral hypoperfusion may be accompanied by myoclonic jerks.
Previous studies investigating autonomic cardiovascular control in elderly persons usually included analysis of R-R interval but not of blood pressure variability. "Physiological" blood pressure rise during the aging process was not accounted for as a possible confounding factor. This study was designed to characterize the relationship between age and short-term heart rate (HR) and blood pressure (BP) variability, independently of the "physiological" rise in BP associated to aging. The study was carried out in 65 "normotensive" (BP< or =140/80 mm Hg) healthy subjects, ranging in age from 18 to 80 years. BP and HR were recorded at rest with a Finapres device. Low-frequency (LF = 0.066 to 0.129 Hz) and high-frequency (HF = respiratory peak +/-0.05 Hz) components of HR and BP variability were assessed using fast-Fourier spectral analysis. Transfer-function analysis between systolic BP and HR variability permitted the calculation of the gain of baroreflex sensitivity. Significant results of this study include a continuous and linear decline with age of normalized LF spectral power of HR in the standing position and of normalized HF spectral power of HR during paced breathing. No correlation was found between age and BP variability, except for LF diastolic BP spectral power in the standing position. The baroreflex gain was negatively correlated with age. The effect of aging on autonomic nervous system cardiac control is progressive and continuous throughout an 18-80 years age range. Although the aging process diminished HR variability and diastolic BP variability, it had no influence on systolic BP variability.
We believe that the pattern of blood pressure response to tilt during the time preceding the development of the vasovagal reaction may provide adjunctive diagnostic information. A group of 101 consecutive patients affected by syncope of uncertain origin underwent passive tilt testing for 45 min at 60 degrees followed, if negative, by oral (sublingual) trinitroglycerin (TNG) 0.4 microg with continuation of the test for 20 min. Three main patterns were observed: the classic (vasovagal) syncope pattern was observed in 36 patients who, during the preparatory phase, had a rapid and full compensatory reflex adaptation to upright position, resulting in stabilization of their blood pressure values until abrupt onset of the vasovagal reaction; the dysautonomic (vasovagal) syncope pattern was observed in 47 patients in whom steady-state adaptation to upright position was not possible. There was thus a progressive fall in their blood pressure until the occurrence of a typical vasovagal reaction; the orthostatic intolerance pattern was observed in 18 patients in whom there was a progressive fall in blood pressure, similar to that of the dysautonomic group, but this was not followed by a clear vasovagal reaction. Compared with the classic, the dysautonomic patients were older, had a higher prevalence of co-morbidities, a very much shorter history of syncopal episodes, and a prevalence of mixed and vasodepressor forms of the VASIS classification. The patients with orthostatic intolerance had clinical characteristics similar to the dysautonmic group but they could not be classified according to the VASIS classification. In conclusion, in patients with syncope, a variety of abnormal responses is observed during tilt testing, suggesting that different syndromes can be diagnosed by the test. A more detailed, although still arbitrary, classification may form the basis of a number of future drug and pacemaker trials, as well as help towards a greater understanding of the different mechanisms of tilt-induced syncope.
Aims
Tilt testing (TT) is recognized to be a valuable contribution to the diagnosis and the pathophysiology of vasovagal syncope (VVS). This study aimed to assess the influence of age on TT responses by examination of a large patient cohort.
Methods and results
Retrospective data from three experienced European Syncope Units were merged to include 5236 patients investigated for suspected VVS by the Italian TT protocol. Tilt testing-positivity rates and haemodynamics were analysed across age-decade subgroups. Of 5236 investigated patients, 3129 (60%) had a positive TT. Cardioinhibitory responses accounted for 16.5% of positive tests and were more common in younger patients, decreasing from the
age of 50–59 years. Vasodepressor (VD) responses accounted for 24.4% of positive tests and prevailed in older patients, starting from the age of 50–59. Mixed responses (59.1% of cases) declined slightly with increasing age. Overall, TT positivity showed a similar age-related trend (P = 0.0001) and was significantly related to baseline systolic
blood pressure (P < 0.001). Tilt testing was positive during passive phase in 18% and during nitroglycerine (TNG)-potentiated phase in 82% of cases. Positivity rate of passive phase declined with age (P = 0.001), whereas positivity rate during TNG remained quite stable. The prevalence of cardioinhibitory and VD responses was similar
during passive and TNG-potentiated TT, when age-adjusted.
Conclusions
Age significantly impacts the haemodynamic pattern of TT responses, starting from the age of 50. Conversely, TT phase—passive or TNG-potentiated—does not significantly influence the type of response, when age-adjusted. Vagal hyperactivity dominates in younger patients, older patients show tendency to vasodepression.
Rationale: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope (T-VVS) requires methods that reflect BP physiology accurately.
Objective: To assess the relative contributions of cardioinhibition and vasodepression to T-VVS using novel methods.
Methods and Results: We studied the parameters determining BP, i.e. stroke volume (SV), heart rate (HR) and total peripheral resistance (TPR), in 163 patients with T-VVS documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of a heart rate decrease (HR) before syncope, and used logarithms of SV-, HR- and TPR-ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined three stages before syncope and two after it based on direction changes of these parameters. The earliest BP decrease occurred nine minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 s. before syncope. At that time SV had a strong negative effect on BP, TPR a lesser negative effect, while HR had increased (all p<0.001). At the onset of cardioinhibition, median HR was at 98 bpm higher than baseline. Cardioinhibition thus initially only represented a reduction of the corrective HR increase, but was nonetheless accompanied by an immediate acceleration of the ongoing BP decrease. At syncope, SV and HR contributed similarly to the BP decrease (p<0.001), while TPR did not affect BP.
Conclusions: The novel methods allowed the relative effects of SV, HR and TPR on BP to be assessed separately, even though all act together. The two major factors lowering BP in T-VVS were reduced SV and cardioinhibition. We suggest that the term 'vasodepression' in reflex syncope should not be limited to reduced arterial vasoconstriction, reflected in TPR, but should also encompass venous pooling, reflected in SV.
New findings:
What is the central question of this study? Pulse contour analysis of the finger arterial pressure by Windkessel modelling is commonly used to estimate stroke volume continuously. But is it valid during dynamic changes in blood pressure? What is the main finding and its importance? Second-by-second analysis revealed that pulse contour analysis underestimated stroke volume by up to 25% after standing from a squat, and 16% after standing thigh-cuff release, when compared with aortic Doppler ultrasound estimates. These results reveal that pulse contour analysis of stroke volume should be interpreted with caution during rapid changes in physiological state.
Abstract:
Dynamic measurements of stroke volume (SV) and cardiac output provide an index of central haemodynamics during transitional states, such as postural changes and onset of exercise. The most widely used method to assess dynamic fluctuations in SV is the Modelflow method, which uses the arterial blood pressure waveform along with age- and sex-specific aortic properties to compute beat-to-beat estimates of aortic flow. Modelflow has been validated against more direct methods in steady-state conditions, but not during dynamic changes in physiological state, such as active orthostatic stress testing. In the present study, we compared the dynamic SV responses from Modelflow (SVMF ), aortic Doppler ultrasound (SVU/S ) and bioelectrical impedance analysis (SVBIA ) during two different orthostatic stress tests, a squat-to-stand (S-S) transition and a standing bilateral thigh-cuff release (TCR), in 15 adults (six females). Second-by-second analysis revealed that when compared with estimates of SV by aortic Doppler ultrasound, Modelflow underestimated SV by up to 25% from 3 to 11 s after standing from the squat position and by up to 16% from 3 to 7 s after TCR (P < 0.05). The SVMF and SVBIA were similar during the first minute of the S-S transition, but were different 3 s after TCR and at intermittent time points between 34 and 44 s (P < 0.05). These findings indicate that the physiological conditions elicited by orthostatic stress testing violate some of the inherent assumptions of Modelflow and challenge models used to interpret bioelectrical impedance responses, resulting in an underestimation in SV during rapid changes in physiological state.
Autonomic support of blood pressure increases with age in humans. Large differences exist in the dose of trimethaphan (TMP) required for ganglionic blockade in young and older women. We asked whether differences in the dose of TMP required to achieve ganglionic blockade are because of differences in the relative contributions of the sympathetic and parasympathetic nervous system in control of blood pressure with age. Muscle sympathetic nerve activity (microneurography, peroneal nerve), heart rate (HR), and blood pressure were recorded before and during incremental doses of TMP camsylate until ganglionic blockade was achieved (absence of muscle sympathetic nerve activity and <5-bpm increase in HR during a valsalva maneuver; final TMP dose, 1-7 mg/min). HR variability was analyzed from the ECG waveform (WinCPRS). The dose of TMP required to achieve ganglionic blockade is positively related to basal HR variability, where women with high HR variability require a higher dose of TMP to achieve ganglionic blockade. In contrast, baseline muscle sympathetic nerve activity is inversely related with the dose of TMP required to achieve ganglionic blockade, such that women with high basal muscle sympathetic nerve activity required a lower dose of TMP. As such, the change in HR with ganglionic blockade was positively related, and the change in mean arterial pressure was inversely related, with the dose of TMP required to achieve ganglionic blockade. These data suggest loss of parasympathetic tone and increased sympathetic tone with aging contribute to the increase in blood pressure with age in women and dictate the dose of TMP that is necessary to achieve ganglionic blockade.
Objectives
The purpose of this study was to investigate the relationship between the onset of asystole and transient loss of consciousness (TLOC) in tilt-induced reflex syncope and estimate how often asystole was the principal cause of TLOC.
Background
The presence of asystole in vasovagal syncope (VVS) may prompt physicians to consider pacemaker therapy for syncope prevention, but the benefit of pacing is limited in VVS.
Methods
We evaluated electrocardiography, electroencephalography, blood pressure, and clinical findings during tilt-table tests. Inclusion required TLOC (video), electroencephalographic slowing, accelerating blood pressure decrease, and an RR interval ≥3 s. We excluded cases with nitroglycerin provocation. Asystole after onset of TLOC (group A) or within 3 seconds before TLOC (group B) was unlikely to cause TLOC, but an earlier start of asystole (group C) could be the cause of TLOC.
Results
In one-third of 35 cases (groups A [n = 9] and B [n = 3]), asystole was unlikely to be the primary cause of TLOC. The median of the mean arterial pressure at the onset of asystole was higher when asystole occurred early (45.5 mm Hg, group C) than when it occurred late (32.0 mm Hg, groups A and B), which suggests that vasodepression was not prominent at the start of asystole in early asystole, further suggesting that early asystole was the prime mechanism of syncope.
Conclusions
In one-third of cases of tilt-induced asystolic reflex syncope, asystole occurred too late to have been the primary cause of TLOC. Reliance on electrocardiography data only is likely to overestimate the importance of asystole.
A classification of vasovagal syncope is proposed on the basis of recordings of arterial pressure and heart rate during tilt-induced syncope. These include mixed, two subdivisions of cardioinhibition and vasodepression categories. There are exceptions to these fundamental groups which are chronotropic incompetence and excessive heart rate rise during tilt and positive carotid sinus massage. They are chosen to illustrate overlap between tilt positive patients who have other conditions such as sinus node disease or carotid sinus syndrome. It is hoped to provide a more pathophysiological and less arbitrary basis for future therapeutic studies and to stimulate debate.
Cardiac asystole during HUTT has been described by some investigators as a benign finding with no major sequelae. Our aim in this study is to correlate the severity of clinical symptoms and physiologic findings prior and during the asystole occurrence. This is a retrospective study review of 536 patients who underwent HUTT for dysautonomia symptoms for the last 3 years. HUTT in our institution consists of 10 min in supine, 30 min of head up at 70°, and recline to supine for 10 min. Physiologic parameters recorded include continuous heart rate, BP, cardiac stroke volume, brain blood flow by near-infra red spectroscopy, sympathetic and parasympathetic tones. Patients' complaints and signs during HUTT were recorded. Follow-up was conducted up to 34 months. Cardiac asystole was defined as the absence of ventricular activity for ≥3 s with cessation of BP signal for the same period on the monitor. Of the 536 patients studied, 25 patients developed cardiac asystole (4.7 %). The asystolic group age was 15.1 + 3.8 years and weighed 56.7 + 21 kg. All the patients fainted and were not able to complete the test with average head up time of 13.8 + 7.1 min. The cardiac asystole duration was 9.2 + 5.8 s. Sixteen patients developed convulsions during the asystole. There was sudden intense vagal tone prior to and during the asystole. Brain perfusion was significantly decreased in all the patients after head up and sharply dropped by 20-35 % in patients who developed convulsions. All patients completely recovered their consciousness after reposition to supine. During recovery, there was overshoot of the brain perfusion above the baseline for several minutes and the HR returned to baseline. Follow-up of these patients: only one patient had a single lead pacemaker, otherwise the 24 patients had no cardiac pacing and were treated by medical therapy. During mean follow-up of 19 + 10 months, five patients developed syncope which resolved after optimizing medical therapy. Cardiac asystole due to neurocardiogenic syncope and dysautonomia has high association with brain anoxia that can lead to convulsions. Such patients require intense medical therapy and close observation with possible intervention by cardiac pacing if prolonged asystole occurs. There is a concern of consequence future brain function.
Numerous investigations have been concerned with the effects of acute arrest of cerebral circulation in animals. The earlier workers¹ studied the effects of ligation of the cerebral arteries. More recently, observations have been made on the effects of temporary occlusion of the chief cerebral arteries² and of temporary cessation of the heart beat.³ Using the method of occlusion of the chief cerebral arteries, Sugar and Gerard⁴ measured the survival time for different regions of the cat brain by the persistence of spontaneous action potentials. A careful study of the changes in function and structure of the brain of the cat resulting from temporary occlusion of the pulmonary artery was reported on by Weinberger, Gibbon and Gibbon.⁵ These methods involved one or another of the following complications: anesthesia; surgical procedures at the time of arrest of circulation in the brain; incomplete arrest of circulation as a
An electrophysiological study of sinus node function, including measurements of resting heart rate, maximal corrected sinus node recovery time and sinoatrial conduction time, was performed in 30 patients, 12–79 years of age, without any clinical, electro car diographic or electrophy siological evidence of sinus node disease.
To analyse autonomic influences, variables were measured before and after sympathetic and parasympathetic blockade. No significant correlations were observed between age and electrophysiological measurements of sinus node function at the control study or after sympathetic blockade. In contrast, the electrophysiological parameters of intrinisic sinus node activity were correlated with age and showed a progressive lengthening of mean sinus cycle length, of maximal corrected sinus node recovery time and of sinoatrial conduction time.
In addition, measurements after vagolysis suggest a progressive decrease of parasympathetic activity with increasing age.
These data also indicate that the respective role of the two components of the autonomic nervous system vary with increasing age: parasympathetic activity predominates in younger subjects; sympathetic and parasympathetic tones are equilibrated in older subjects.
The normal sinus node function represents an equilibrated system: in parallel with ageing of the intrinsic properties of the sinus node, parasympathetic activity decreases so that basal properties remain stable throughout life.
The cardiovascular responses to postural change, and how they are affected by aging, are inadequately described in women. Therefore, the authors examined the influence of age and sex on the responses of blood pressure, cardiac output, heart rate, and other variables to change in posture. Measurements were made after 10 minutes each in the supine, seated, and standing positions in 22 men and 25 women who ranged in age from 21 to 59 years. Several variables differed, both by sex and by age, when subjects were supine. On rising, subjects' diastolic and mean arterial pressures, heart rate, total peripheral resistance (TPR), and thoracic impedance increased; cardiac output, stroke volume, and mean stroke ejection rate decreased; and changes in all variables, except heart rate, were greater from supine to sitting than sitting to standing. The increase in heart rate was greater in the younger subjects, and increases in TPR and thoracic impedance were greater in the older subjects. Stroke volume decreased less, and TPR and thoracic impedance increased more, in the women than in the men. The increase in TPR was particularly pronounced in the older women. These studies show that the cardiovascular responses to standing differ, in some respects, between the sexes and with age. The authors suggest that the sex differences are, in part, related to greater decrease of thoracic blood volume with standing in women than in men, and that the age differences result, in part, from decreased responsiveness of the high-pressure baroreceptor system.
Determination of whether results of cardiovascular reflex tests and spectral analysis of heart rate variability are age dependent and whether there is correlation between results of both, cardiovascular reflex tests (the Valsalva manoeuvre, deep breathing test, handgrip test, cold face stimulus test, orthostatic test) and spectral analysis of heart rate variability were performed on 83 healthy volunteers of both genders, aged 21 to 70 years. We found that results of all heart rate based tests and results of spectral analysis decreased with aging, while results of blood pressure based tests did not. Parasympathetic activity predominated in younger subjects, while in older subjects sympathetic activity was dominant. Valsalva, deep breathing, and orthostatic ratios correlated with integrals of amplitude spectra in the standing posture and deep breathing and cold face stimulus ratios with integrals of amplitude spectra in the supine posture, whereas blood pressure changes during handgrip and orthostatic test did not correlate with integrals of the amplitude spectra. These findings suggest that tests based on heart rate may be more sensitive than tests based on blood pressure changes. This study supports the use of spectral analysis as an additional clinical test of autonomic nervous system function and stresses the importance of age in the evaluation of the results of autonomic nervous system function testing.
Because of its episodic behavior, the correlation of spontaneous syncope with an abnormal finding can be considered a reference standard.
We inserted an implantable loop recorder in 111 patients with syncope, absence of significant structural heart disease, and a normal ECG; tilt-testing was negative in 82 (isolated syncope) and positive in 29 (tilt-positive). The patients had had >/=3 episodes of syncope in the previous 2 years and were followed up for 3 to 15 months. Results were similar in the isolated syncope group and the tilt-positive group: syncope recurred in 28 (34%) and 10 patients (34%), respectively, and electrocardiographic correlation was found in 24 (23%) and 8 (28%) patients, respectively. The most frequent finding, which was recorded in 46% and 62% of patients, respectively, was one or more prolonged asystolic pauses, mainly due to sinus arrest, preceded for a few minutes by progressive bradycardia or progressive tachycardia-bradycardia. Bradycardia without pauses was observed in 8% and 12% of cases, respectively. The remaining patients had normal sinus rhythm or sinus tachycardia, except for one, who had ectopic atrial tachycardia. In the tilt-positive group, an asystolic syncope was also recorded when the type of response to tilt-testing was vasodepressor or mixed. Presyncopal episodes were never characterized by asystolic pauses; normal sinus rhythm was the most frequent finding.
Homogeneous findings were observed during syncope. In most patients, the likely cause was neurally-mediated, and the most frequent mechanism was a bradycardic reflex. In the other cases, a normal sinus rhythm was frequently recorded. Presyncope was not an accurate surrogate for syncope in establishing a diagnosis.
We sought to determine whether there are age-related differences in vasovagal syncope.
In those with suspected vasovagal (neurocardiogenic) syncope, tilt testing demonstrates different hemodynamic responses. These responses may be age related, reflecting differing underlying pathophysiology.
Using a two-stage tilt protocol with glyceryl trinitrate (GTN) provocation, 505 consecutive syncopal patients were studied. Their baseline characteristics and hemodynamic responses during both early and tilt-induced collapse were analyzed. Hemodynamic responses were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed, cardioinhibition, severe cardioinhibition/asystole, pure vasodepression, chronotropic incompetence, and excessive heart rate rise. Multivariate regression analyses were performed to determine the associations of the baseline clinical characteristics (including age) and the tilt-induced hemodynamic responses.
Thirty-three patients were unable to tolerate tilt testing. Age was independently associated with distinct responses during tilt. Chronotropic incompetence was predicted by increasing age (odds ratio [OR] 1.04, p < 0.0002). Younger age predicted an excessive heart rate rise (OR 0.97, p < 0.0005). Pure vasodepression was more common in the older group (>65 years; OR 29.5, p < 0.0001), whereas severe cardioinhibition was much less common in the older age group (OR 0.18, p < 0.0001).
There appear to be distinct pathophysiologies underlying vasovagal syncope in different age groups. Young people appear to have excessive cardiac and autonomic responses to stress, whereas older patients appear to have a more generalized cardiovascular decline, with attenuated cardiac and autonomic responses to stress.
The aim of the present study was to assess the cardiovascular autonomic function and responses to tilt test in young and elderly patients with syncope of unknown origin. We evaluated two groups of patients with previous unexplained syncope: 192 older subjects (112 males, 80 females, mean age 67.2 +/- 6.8 years) and 188 young subjects (102 males, 86 females, mean age 25 +/- 9 years). All patients underwent ambulatory electrocardiogram (ECG) monitoring, to evaluate time domain indices of heart rate variability (HRV), and head-up tilt test in the morning after an overnight fast. The responses of positive tilt test were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed (VASIS-1), cardioinhibition (VASIS-2A), severe cardioinhibition/asystole (VASIS-2B), pure vasodepression (VASIS-3). All the time-domain HRV indexes were lower in the older than in young subjects. The rate of positive responses was not different in the two groups. In elderly group the positive head-up tilt test responses showed: a pure vasodepressive response (VASIS 3) in 126 patients (65%), a mixed (VASIS-1) response in 25 patients (13%), a cardioinhibitory (VASIS-2A) response in 13 patients (7%). Only 28 (14.6%) of elderly group patients had negative head-up tilt test response. In contrast, in young group the positive head-up tilt test responses showed: 114 patients (61.2%) a mixed (VASIS-1) vasovagal response, 40 patients (22.3%) a cardioinhibitory (VASIS-2A) response, four (2.1%) patients a severe cardioinhibitory (VASIS-2B) and four (2.1%) patients a pure vasodepression (VASIS-3) response, respectively. The tilt test was negative in response in 26 young patients (12.2%). Our results confirm that the head-up tilt test may be useful in assessing unexplained syncope, since it is seen to be positive in 85% of elderly patients and 86% in young patients. In our subjects, vasodepressive response was the most frequent cause of syncope in older subjects, while vasovagal response is the commonest cause of syncope of young patients. This different behaviour in the elderly may be is explained with physiological aging, which is associated with a reduction of sympathetic-parasympathetic control on the cardiac rhythm, demonstrated by reduction in all the time domain HRV indices.