Pathophysiology of Syncope:Current Concepts and Their Development.

Syncope is a symptom in which transient loss of consciousness occurs as a consequence of a self-limited, spontaneously-terminating, period of cerebral hypoperfusion. Many circulatory disturbances (e.g. brady- or tachyarrhythmias, reflex cardioinhibition-vasodepression-hypotension) may trigger a syncope or near-syncope episode, and identifying the cause(s) is often challenging. Some syncope may involve multiple etiologies operating in concert, whereas in other cases multiple syncope events may be due to various differing causes at different times. In this communication we address current understanding of the principal contributors to syncope pathophysiology including examination of the manner in which concepts evolved, and an overview of factors that constitute consciousness and loss of consciousness, and aspects of neural-vascular control and communication that are impacted by cerebral hypo perfusion leading to syncope . Emphasis focuses on: 1) current understanding of the way transient systemic hypotension impacts brain blood flow and brain function, 2) the complexity and temporal sequence of vascular, humoral and cardiac factors that may accompany the most common causes of syncope, 3) the range of circumstances and disease states that may lead to syncope, and 4) clinical features associated with syncope and in particular the reflex syncope syndromes.

Percutaneous Left Atrial Appendage Occlusion Therapy: Evolution and Growing Evidence.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and if untreated, significantly increases both the risk of intracardiac thrombus formation and ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been estimated to be the source of thrombus development in 91% to 99% of cases. Consequently, oral anticoagulation (OAC) to provide stroke prevention has become the standard of care for most AF patients; however, OACs are associated with a risk of bleeding and their efficacy depends on optimal patient compliance. In terms of alternative approaches to preventing embolic events, surgical LAA excision was attempted as early as in the late 1940s in patients with valvular AF; LAA excision remains a recommendation in surgical guidelines for NVAF patients who need open-heart coronary bypass or valvular replacement/repair surgeries. However, due to its invasive nature surgical LAA intervention has limited clinical application in present cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention; this is particularly the case in patients at increased bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception some twenty years ago. Herein we systematically review both the critical literature that led to the development of LAAO, and the increasing clinical evidence supporting the application of this treatment strategy in NVAF. To this end we focus on recently published critical evaluations of United States Food and Drug Administration (US FDA) and Conformité Européenne (Commercial Sale of Licensed Product in the EU) (CE-Mark) approved LAAO devices, summarize the current status of LAAO therapy, and discuss the future perspectives regarding the knowledge and technology gaps in this area by recognizing the potential contributions of many ongoing but likely transformative clinical trials.

Variability of cardioinhibition in vasovagal syncope: differences between subgroups during cardioinhibition and beyond.

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.

Novel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal Syncope.

RATIONALE: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope requires methods that reflect BP physiology accurately. OBJECTIVE: To assess the relative contributions of cardioinhibition and vasodepression to tilt-induced vasovagal syncope using novel methods. METHODS AND RESULTS: We studied the parameters determining BP, that is, stroke volume (SV), heart rate (HR), and total peripheral resistance (TPR), in 163 patients with tilt-induced vasovagal syncope documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of an HR decrease (HR) before syncope and used logarithms of SV, HR, and TPR ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined 3 stages before syncope and 2 after it based on direction changes of these parameters. The earliest BP decrease occurred 9 minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 seconds 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, the 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, although all act together. The 2 major factors lowering BP in tilt-induced vasovagal syncope 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.

Inappropriate sinus tachycardia: an examination of existing definitions.

AIMS: Inappropriate sinus tachycardia (IST) is a syndrome characterized by an elevated sinus rate unassociated with known physiological, pathological, or pharmacological causes. Despite published consensus documents, IST definitions appear to vary in the literature. In this study, we reviewed IST publications to evaluate IST definition variability and ascertain the degree to which consensus definitions are being adopted. METHODS AND RESULTS: English-language articles in PubMed, Ovid MEDLINE, Ovid Embase, and Google Scholar published from 1 January 1970 to 1 June 2021 with the title terms 'inappropriate sinus tachycardia,' 'non-paroxysmal sinus tachycardia,' or 'permanent sinus tachycardia' were searched. In each, the IST definition used, qualifying characteristics, and publications cited to support each definition were recorded. We identified 138 publications meeting the search criteria. Inappropriate sinus tachycardia definitions were provided in 114 of 138 articles (83%). A majority of definitions (92/114, 81%) used distinct heart rate (HR) thresholds. Among these, the most common threshold was ≥100 beats per minute (BPM) (75/92, 82%), mainly measured at rest (54/92, 59%). Most definitions (47/92, 51%) included a second criterion to qualify for IST; these were most often an HR threshold of 90 BPM measured over 24 h by ambulatory electrocardiogram (37/47, 79%). Diagnosis of exclusion was a common criterion (75/92, 82%) but symptom status was not (41/92, 45%). The 2015 Heart Rhythm Society IST consensus was commonly cited but adopted in only 37% of definitions published after 2015. CONCLUSIONS: Inappropriate sinus tachycardia definitions in current literature are inconsistent, and professional society consensus IST definitions have, to date, had limited impact.

Tilt testing remains a valuable asset.

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.

Timing of syncope in ictal asystole as a guide when considering pacemaker implantation.

INTRODUCTION: In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. METHODS: In this retrospective cohort study, we searched video-EEG databases for individuals with focal seizures and IA (asystole ≥ 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting ≤3 s before syncope onset, or after syncope began, could not have been the dominant cause. RESULTS: We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5-32] vs. 5 [range: 3-9] s; p < .001) and those with the patient seated vs. supine (79% vs. 46%; p = .049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. CONCLUSIONS: In IA, cardioinhibition played an important role in most seizure-induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA.

A randomized study of yoga therapy for the prevention of recurrent reflex vasovagal syncope.

AIMS: Vasovagal syncope (VVS) is a common cardiovascular dysautonomic disorder that significantly impacts health and quality of life (QoL). Yoga has been shown to have a positive influence on cardiovascular autonomics. This study assessed the effectiveness of yoga therapy on the recurrence of VVS and QoL. METHODS AND RESULTS: We randomized subjects with recurrent reflex VVS (>3 episodes in the past 1 year) and positive head-up tilt test to guideline-directed therapy (Group 1) or yoga therapy (Group 2). Patients in Group 1 were advised guideline-directed treatment and Group 2 was taught yoga by a certified instructor. The primary endpoint was VVS recurrences and QoL. Between June 2015 and February 2017, 97 highly symptomatic VVS patients were randomized (Group 1: 47 and Group 2: 50). The mean age was 33.1 ± 16.6 years, male:female of 40:57, symptom duration of 17.1 ± 20.7 months, with a mean of 6.4 ± 6.1 syncope episodes. Over a follow-up of 14.3 ± 2.1 months Group 2 had significantly lower syncope burden compared with Group 1 at 3 (0.8 ± 0.9 vs. 1.8 ± 1.4, P < 0.001), 6 (1.0 ± 1.2 vs. 3.4 ± 3.0, P < 0.001), and at 12 months (1.1 ± 0.8 vs. 3.8 ± 3.2, P < 0.001). The Syncope functional score questionnaire was significantly lower in Group 2 compared with Group 1 at 3 (31.4 ± 7.2 vs. 64.1 ± 11.5, P < 0.001), 6 (26.4 ± 6.3 vs. 61.4 ± 10.7, P < 0.001), and 12 months (22.2 ± 4.7 vs. 68.3 ± 11.4, P < 0.001). CONCLUSION: For patients with recurrent VVS, guided yoga therapy is superior to conventional therapy in reducing symptom burden and improving QoL.

Sinus arrest: A rare observation during radiofrequency ablation along the coronary sinus roof.

Catheter-based radiofrequency (RF) ablation targeting segments of the cardiac conduction system and/or selected regions of myocardium is an accepted treatment for many cardiac arrhythmias. On the other hand, while purposeful extension of RF ablation to include nearby cardiac neural elements, particularly epicardial ganglionated plexi (GP), remains a subject of ongoing study, inadvertent stimulation of such structures may occur during an otherwise conventional RF ablation procedure. Thus, asystolic pauses have been observed during RF ablation of left ventricular free-wall accessory pathways, slow AV node pathways, and the left superior pulmonary vein. In this report, sinus arrest occurred within 3.3 s of RF application (40 W at 50°C) along the coronary sinus roof for treatment of an atypical "slow-slow" atrioventricular nodal reentrant tachycardia. Energy delivery was immediately terminated, but asystole persisted for 4.7 s followed by sinus bradycardia. The procedure was temporarily halted, but later was successfully resumed. Given the latency from terminating RF to return of sinus node function, the sinus arrest was likely a centrally mediated reflex vagal response. Consequently, while parasympathetic ganglia near the CS os are believed to principally innervate the AV node, not the sinus node, our observation highlights the neural cross-communications that likely exist in this region of the heart.

A higher proportion of men than of women fainted in the phase without nitroglycerin in tilt-induced vasovagal syncope.

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 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 nitroglycerin p = 0.003; with nitroglycerin p = 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.