Will Artificial Intelligence Be "Better" Than Humans in the Management of Syncope?

Clinical decision-making regarding syncope poses challenges, with risk of physician error due to the elusive nature of syncope pathophysiology, diverse presentations, heterogeneity of risk factors, and limited therapeutic options. Artificial intelligence (AI)-based techniques, including machine learning (ML), deep learning (DL), and natural language processing (NLP), can uncover hidden and nonlinear connections among syncope risk factors, disease features, and clinical outcomes. ML, DL, and NLP models can analyze vast amounts of data effectively and assist physicians to help distinguish true syncope from other types of transient loss of consciousness. Additionally, short-term adverse events and length of hospital stay can be predicted by these models. In syncope research, AI-based models shift the focus from causality to correlation analysis between entities. This prompts the search for patterns rather than defining a hypothesis to be tested a priori. Furthermore, education of students, doctors, and health care providers engaged in continuing medical education may benefit from clinical cases of syncope interacting with NLP-based virtual patient simulators. Education may be of benefit to patients. This article explores potential strengths, weaknesses, and proposed solutions associated with utilization of ML and DL in syncope diagnosis and management. Three main topics regarding syncope are addressed: 1) clinical decision-making; 2) clinical research; and 3) education. Within each domain, we question whether "AI will be better than humans," seeking evidence to support our objective inquiry.

Loss of plasticity in deep continual learning.

Artificial neural networks, deep-learning methods and the backpropagation algorithm1 form the foundation of modern machine learning and artificial intelligence. These methods are almost always used in two phases, one in which the weights of the network are updated and one in which the weights are held constant while the network is used or evaluated. This contrasts with natural learning and many applications, which require continual learning. It has been unclear whether or not deep learning methods work in continual learning settings. Here we show that they do not-that standard deep-learning methods gradually lose plasticity in continual-learning settings until they learn no better than a shallow network. We show such loss of plasticity using the classic ImageNet dataset and reinforcement-learning problems across a wide range of variations in the network and the learning algorithm. Plasticity is maintained indefinitely only by algorithms that continually inject diversity into the network, such as our continual backpropagation algorithm, a variation of backpropagation in which a small fraction of less-used units are continually and randomly reinitialized. Our results indicate that methods based on gradient descent are not enough-that sustained deep learning requires a random, non-gradient component to maintain variability and plasticity.

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.

Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias. a scientific statement of the european heart rhythm association (ehra) of the esc, the heart rhythm society (hrs), the asia pacific heart rhythm society (aphrs) and the latin american heart rhythm society (lahrs)

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Off-Policy Prediction Learning: An Empirical Study of Online Algorithms.

Off-policy prediction-learning the value function for one policy from data generated while following another policy-is one of the most challenging problems in reinforcement learning. This article makes two main contributions: 1) it empirically studies 11 off-policy prediction learning algorithms with emphasis on their sensitivity to parameters, learning speed, and asymptotic error and 2) based on the empirical results, it proposes two step-size adaptation methods called and that help the algorithm with the lowest error from the experimental study learn faster. Many off-policy prediction learning algorithms have been proposed in the past decade, but it remains unclear which algorithms learn faster than others. In this article, we empirically compare 11 off-policy prediction learning algorithms with linear function approximation on three small tasks: the Collision task, the task, and the task. The Collision task is a small off-policy problem analogous to that of an autonomous car trying to predict whether it will collide with an obstacle. The and tasks are designed such that learning fast in them is challenging. In the Rooms task, the product of importance sampling ratios can be as large as 214 . To control the high variance caused by the product of the importance sampling ratios, step size should be set small, which, in turn, slows down learning. The task is more extreme in that the product of the ratios can become as large as 214 × 25 . The algorithms considered are Off-policy TD, five Gradient-TD algorithms, two Emphatic-TD algorithms, Vtrace, and variants of Tree Backup and ABQ that are applicable to the prediction setting. We found that the algorithms' performance is highly affected by the variance induced by the importance sampling ratios. Tree Backup, Vtrace, and ABTDare not affected by the high variance as much as other algorithms, but they restrict the effective bootstrapping parameter in a way that is too limiting for tasks where high variance is not present. We observed that Emphatic TDtends to have lower asymptotic error than other algorithms but might learn more slowly in some cases. Based on the empirical results, we propose two step-size adaptation algorithms, which we collectively refer to as the Ratchet algorithms, with the same underlying idea: keep the step-size parameter as large as possible and ratchet it down only when necessary to avoid overshoot. We show that the Ratchet algorithms are effective by comparing them with other popular step-size adaptation algorithms, such as the Adam optimizer.

Orthostatic hypotension is associated with higher levels of circulating endostatin.

Aims: The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation. Methods and results: We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, P < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (P < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors. Conclusion: Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.

Making certain that noninvasive therapy for vasovagal syncope has failed before proceeding to invasive interventions.

There is a perceived need to express concisely the advice of guidelines in the context of consideration of invasive management of highly symptomatic vasovagal syncope. In response to this need the table is presented as a checklist and the text adds explanation and details. It is anticipated that this will prove to be of value for clinicians.

JAK/STAT signaling pathway affects CCR5 expression in human CD4+ T cells.

CCR5 serves as R5-tropic HIV co-receptor. Knocking out CCR5 in HIV patients, which has occurred <10 times, is believed important for cure. JAK/STAT inhibitors tofacitinib and ruxolitinib inhibit CCR5 expression in HIV+ viremic patients. We investigated the association of JAK/STAT signaling pathway with CCR5/CCR2 expression in human primary CD4+ T cells and confirmed its importance. Six of nine JAK/STAT inhibitors that reduced CCR5/CCR2 expression were identified. Inhibitor-treated CD4+ T cells were relatively resistant, specifically to R5-tropic HIV infection. Furthermore, single JAK2, STAT3, STAT5A, and STAT5B knockout and different combinations of JAK/STAT knockout significantly reduced CCR2/CCR5 expression of both RNA and protein levels, indicating that CCR5/CCR2 expression was positively regulated by JAK-STAT pathway in CD4+ T cells. Serum and glucocorticoid-regulated kinase 1 (SGK1) knockout affected CCR2/CCR5 gene expression, suggesting that SGK1 is involved in CCR2/CCR5 regulation. If cell surface CCR5 levels can be specifically and markedly down-regulated without adverse effects, that may have a major impact on the HIV cure agenda.

Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden.

Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.

Tilt table testing, methodology and practical insights for the clinic.

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.

Familial risk of vasospastic angina: a nationwide family study in Sweden.

OBJECTIVES: Vasospastic angina (VSA) is a complex coronary vasomotor disorder associated with an increased risk of myocardial infarction and sudden death. Despite considerable advances in understanding VSA pathophysiology, the interplay between genetic and environmental factors remains elusive. Accordingly, we aimed to determine the familial VSA risk among first-degree relatives of affected individuals. METHODS: A population-based multigenerational cohort study was conducted, including full-sibling pairs born to Swedish parents between 1932 and 2018. Register-based diagnoses were ascertained through linkage to the Swedish Multigeneration Register and National Patient Register. Incidence rate ratios (IRRs) and adjusted HRs were calculated for relatives of individuals with VSA compared with relatives of individuals without VSA. RESULTS: The total study population included 5 764 770 individuals. Overall, 3461 (0.06%) individuals (median age at disease onset 59 years, IQR: 63-76) were diagnosed with VSA. Of these, 2236 (64.61%) were women. The incidence rate of VSA for individuals with an affected sibling was 0.31 (95% CI: 0.24 to 0.42) per 1000 person-years compared with 0.04 (95% CI: 0.04 to 0.04) per 1000 person-years for those without an affected sibling, yielding an IRR of 7.58 (95% CI: 5.71 to 10.07). The risk of VSA for siblings with an affected sibling was significantly increased in the fully adjusted model (HR: 2.56; 95% CI: 1.73 to 3.79). No increased risk of VSA was observed in spouses of affected individuals (HR: 0.63; 95% CI: 0.19 to 2.09). CONCLUSIONS: In this nationwide family study, we identified high familial risk for VSA independent of shared environmental risk factors. Our findings indicate that VSA tends to cluster in families, emphasising the need to explore genetic and non-genetic factors that may contribute.

Tilt testing.

Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving sublingual nitroglycerine after 15 min, while monitoring beat-to-beat blood pressure (BP) and recording on video. Tilt testing is time-consuming but it is clinically useful and can guide therapy. Complications are rare. Syncope types include vasovagal syncope where BP falls after >3 min of tilt-up and later the heart rate falls; classic orthostatic hypotension where there is an immediate, progressive BP fall with minimal heart rate change; delayed orthostatic hypotension with a late BP fall after a stable phase but little or no heart rate rise; psychogenic pseudosyncope with apparent loss of consciousness, but no BP fall and a moderate heart rate rise; and postural orthostatic tachycardia syndrome where there is a significant heart rate rise but no BP fall.

Definitive aetiology of unexplained syncope after cardiovascular autonomic tests in a tertiary syncope unit.

AIMS: Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. METHODS AND RESULTS: Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. CONCLUSION: A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.

Twenty-five years of research on syncope.

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.

Correlation of a commercial platform's results with post-vaccination SARS-CoV-2 neutralizing antibody response and clinical host factors.

INTRODUCTION: The objective of this study was to describe the correlation between the commercially available assay for anti-S1/RBD IgG and protective serum neutralizing antibodies (nAb) against SARS-CoV-2 in an adult population after SARS-CoV-2 vaccination, and determine if clinical variables impact this correlation. METHODS: We measured IgG anti-S1/RBD using the IgG-II CMIA assay and nAb IC50 values against SARS-CoV-2 WA-1 in sera serially collected post-mRNA vaccination in veterans and healthcare workers of the Veterans Affairs Connecticut Healthcare System (VACHS) between December 2020 and January 2022. The correlation between IgG and IC50 was measured using Pearson correlation. Clinical variables (age, sex, race, ethnicity, prior COVID infection defined by RT-PCR, history of malignancy, estimated glomerular filtration rate (GFR calculated using CKD-EPI equation) were collected by manual chart review. The impact of these clinical variables on the IgG-nAb correlation was analyzed first with univariable regression. Variables with a significance of p < 0.15 were analyzed with forward stepwise regression analysis. RESULTS: From 127 sera samples in 100 unique subjects (age 20-93 years; mean 63.83; SD 15.63; 29% female; 67% White), we found a robust correlation between IgG anti-S1/RBD and nAb IC50 (R2 = 0.83, R2adj = 0.70, p < 0.0001). Race, ethnicity, and a history of malignancy were not significant on univariable analysis. GFR (p < 0.05) and prior COVID infection (p < 0.001) had a significant impact on the correlation between IgG anti-S1/RBD and nAb IC50. Age (p = 0.06) and sex (p = 0.07) trended towards significance on univariable analysis, but were not significant on multivariable regression. CONCLUSIONS: There was a strong correlation between IgG anti-S1/RBD and nAb IC50 after SARS-CoV-2 vaccination. Clinical comorbidities, such as prior COVID infection and renal function, impacted this correlation. These results may assist the prediction of post-vaccination immune protection in clinical settings using cost-effective commercial platforms.