Sinus Tachycardia: a Multidisciplinary Expert Focused Review.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Safety, Pharmacokinetic, and Pharmacodynamic Study of a Sublingual Formula for the Treatment of Vasovagal Syncope.

BACKGROUND: Vasovagal syncope is a common cause of syncope which, if recurrent, can have multiple negative consequences such as injury and occupational disability. Various medications can be used to decrease the recurrence of vasovagal syncope but there are no drugs that can be used by patients to interrupt a perceived vasovagal episode. METHODS: A phase I study was performed to evaluate the tolerability and safety of a gel formulation containing capsaicin (1 mg), phenylephrine HCL (PE) and caffeine citrate (200 mg) (CPC) in normal adult volunteers. Secondary objectives were to characterize the pharmacokinetics (PK) of the CPC formulation and the highest dose of PE needed to achieve a target increase in systolic BP of at least 40 mmHg. After receiving the first dose, a second dose of the CPC mixture was administered at 2 h. Suboptimal changes in systolic blood pressure (SBP) were noted at PE doses of 0.6, 1.2, and 1.8 mg, therefore a second cohort was studied at PE doses of 10, 20, and 30 mg. Blood samples were collected in rapid sequence and were assayed for all three drugs. RESULTS: A total of 17 subjects received the drug with no serious adverse effects reported. All doses were well tolerated, although the capsaicin content usually caused expected temporary oral and gastric discomfort. One subject did not complete the study because of a vasovagal reaction that was associated with the frequent blood sampling. There was a 5-25 min lag in the appearance of measurable blood concentrations of capsaicin and phenylephrine. Most subjects had baseline caffeine concentrations from dietary use, with a gradual increase noted after 15 min consistent with GI absorption. Although the intended criterion of a 40 mmHg increase in SBP was not reached, a clinically significant increase in BP for at least 15 min was noted in the six subjects who received the highest dose of PE (30 mg), with a gradual decline over the next 2 h. CONCLUSION: The ternary mixture of capsaicin, phenylephrine, and caffeine was well tolerated when administered as two sublingual/oral doses over a 2-h period.

Persistent Asthma Is Associated With Increased Risk for Incident Atrial Fibrillation in the MESA.

BACKGROUND: Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this association would be attenuated by adjustment for baseline markers of systemic inflammation. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective longitudinal study of adults free of cardiovascular disease at baseline. Presence of asthma was determined at exam 1. Persistent asthma was defined as asthma requiring use of controller medications. Intermittent asthma was defined as asthma without use of controller medications. Participants were followed for a median of 12.9 (interquartile range, 10-13.6) years for incident AF. Multivariable Cox regression models were used to assess associations of asthma subtype and AF. RESULTS: The 6615 participants were a mean (SD) 62.0 (10.2) years old (47% male, 27% black, 12% Chinese, and 22% Hispanic). AF incidence rates were 0.11 (95% CI, 0.01-0.12) events/10 person-years for nonasthmatics, 0.11 (95% CI, 0.08-0.14) events/10 person-years for intermittent asthmatics, and 0.19 (95% CI, 0.120.49) events/10 person-years for persistent asthmatics (log-rank P=0.008). In risk-factor adjusted models, persistent asthmatics had a greater risk of incident AF (hazard ratio, 1.49 [95% CI, 1.03-2.14], P=0.03). IL (Interleukin)-6 (hazard ratio, 1.26 [95% CI, 1.13-1.42]), TNF (tumor necrosis factor)-α receptor 1 (hazard ratio, 1.09 [95% CI, 1.08-1.11]) and D-dimer (hazard ratio, 1.10 [95% CI, 1.02-1.20]) predicted incident AF, but the relationship between asthma and incident AF was not attenuated by adjustment for any inflammation marker (IL-6, CRP [C-reactive protein], TNF-α R1, D-dimer, and fibrinogen). CONCLUSIONS: In a large multiethnic cohort with nearly 13 years follow-up, persistent asthma was associated with increased risk for incident AF. This association was not attenuated by adjustment for baseline inflammatory biomarkers.

Autonomic dysfunction: Diagnosis and management.

The autonomic nervous system is designed to maintain physiologic homeostasis. Its widespread connections make it vulnerable to disruption by many disease processes including primary etiologies such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, and pure autonomic failure and secondary etiologies such as diabetes mellitus, amyloidosis, and immune-mediated illnesses. The result is numerous symptoms involving the cardiovascular, gastrointestinal, and urogenital systems. Patients with autonomic dysfunction (AUD) often have peripheral and/or cardiac denervation leading to impairment of the baroreflex, which is known to play a major role in determining hemodynamic outcome during orthostatic stress and low cardiac output states. Heart rate and plasma norepinephrine responses to orthostatic stress are helpful in diagnosing impairment of the baroreflex in patients with orthostatic hypotension (OH) and suspected AUD. Similarly, cardiac sympathetic denervation diagnosed with MIBG scintigraphy or 18F-DA PET scanning has also been shown to be helpful in distinguishing preganglionic from postganglionic involvement and in diagnosing early stages of neurodegenerative diseases. In this chapter, we review the causes of AUD, the pathophysiology and resulting cardiovascular manifestations with emphasis on the diagnosis and treatment of OH.

ACC/AHA/HRS Versus ESC Guidelines for the Diagnosis and Management of Syncope: JACC Guideline Comparison.

Syncope is a commonly encountered and challenging problem in medical practice. Presentations are variable, and the causal mechanism often remains elusive even after extensive (and often expensive) evaluation. Clinical practice guidelines have been developed to help guide the multidisciplinary approach necessary to diagnose and manage the broad spectrum of patients presenting with syncope. The American College of Cardiology/American Heart Association, in collaboration with the Heart Rhythm Society, published its first syncope guidelines in 2017. The European Society of Cardiology released the fourth iteration of its syncope guidelines in 2018. This review highlights the differences and congruencies between the 2 sets of recommendations, their implications for clinical practice, the remaining gaps in understanding, and areas of future research.

P-Wave Amplitude and PR Changes in Patients With Inappropriate Sinus Tachycardia: Findings Supportive of a Central Mechanism.

BACKGROUND: The mechanism of inappropriate sinus tachycardia (IST) remains incompletely understood. METHODS AND RESULTS: We prospectively compared 3 patient groups: 11 patients with IST (IST Group), 9 control patients administered isoproterenol (Isuprel Group), and 15 patients with cristae terminalis atrial tachycardia (AT Group). P-wave amplitude in lead II and PR interval were measured at a lower and higher heart rate (HR1 and HR2, respectively). P-wave amplitude increased significantly with the increase in HR in the IST Group (0.16±0.07 mV at HR1=97±12 beats per minute versus 0.21±0.08 mV at HR2=135±21 beats per minute, P=0.001). The average increase in P-wave amplitude in the IST Group was similar to the Isuprel Group (P=0.26). PR interval significantly shortened with the increases in HR in the IST Group (146±15 ms at HR1 versus 128±16 ms at HR2, P<0.001). A similar decrease in the PR interval was noted in the Isuprel Group (P=0.6). In contrast, patients in the atrial tachycardia Group experienced PR lengthening during atrial tachycardia when compared with baseline normal sinus rhythm (153±25 ms at HR1=78±17 beats per minute versus 179±29 ms at HR2=140±28 beats per minute, P<0.01). CONCLUSIONS: We have shown that HR increases in patients with IST were associated with an increase in P-wave amplitude in lead II and PR shortening similar to what is seen in healthy controls following isoproterenol infusion. The increase in P-wave amplitude and absence of PR lengthening in IST support an extrinsic mechanism consistent with a state of sympatho-excitation with cephalic shift in sinus node activation and enhanced atrioventricular nodal conduction.

Psychogenic pseudosyncope: Not always a diagnosis of exclusion.

BACKGROUND: Psychogenic pseudosyncope (PPS) frequently mimics syncope. The aim of this study was to assess the prevalence and clinical features of PPS and its relationship to vasovagal syncope (VVS). METHODS: We examined retrospectively the medical records of 1,401 consecutive patients referred to a syncope unit. We identified patients who had the final diagnosis of PPS. In these patients, we retrieved the initial diagnosis made during their first visit and the subsequent tests performed leading to the final diagnosis. RESULTS: Fourteen (1.0%) patients (mean age 35 ± 14; 11 females) were diagnosed as having PPS: seven had a diagnosis of PPS alone and seven had both VVS and PPS. High frequency of attacks (53 ± 35 attacks during the previous year), prolonged loss of consciousness (minutes to > 1 hour), and a history of psychiatric disorders characterized PPS patients. Tilt test reproduced a PPS attack in the presence of normal blood pressure and heart rate in seven patients (50%), and induced VVS in another three patients who had the final diagnosis of both PPS and VVS. In two patients, one or more events occurred during the clinic visits and were directly witnessed by the clinic personnel. CONCLUSIONS: We have shown that 1% of referrals to a syncope unit have the final diagnosis of PPS and that up to 50% of cases presented with a different initial diagnosis, namely VVS. Our findings suggest that causality between syncope and psychiatric disorders is likely bidirectional. The presence of a multidisciplinary team is important to address this often unrecognized relationship.

Emerging concepts in diagnosis and treatment of syncope by pacing.

Neuroendocrine syncope is a newly proposed term to embody both syncope of reflex and adenosine-related etiology. Recent publications on tilt testing have revealed the presence of a hypotensive tendency in some patients, even in the face of severe cardioinhibition. This new understanding may allow better selection of older reflex syncope patients, documented by ECG loop recorder, for successful pacing where tilt testing is ideally negative for a good result in terms of few syncope recurrences and prompts a less aggressive management policy when hypotensive medication is required. Furthermore, plasma adenosine levels not only define a new group of patients who have low adenosine and will respond well to cardiac pacing but also, by assessing adenosine receptor affinity, offer a possible explanation for vasodepression accompanying severe cardioinhibition. The question of the timing of loss of consciousness in reflex syncope needs to be addressed because, if consciousness is lost before asystole, pacing is likely to be ineffective.

Outreach syncope clinic managed by a nurse practitioner: Outcome and cost effectiveness.

Introduction The purpose of this study was to assess the clinical and financial outcomes of a novel outreach syncope clinic. Methods We compared the clinical outcome of the Faint and Fall Clinic at the American Center (January-June 2016) with that of the University of Wisconsin Health and Clinics Faint and Fall Clinic (January 2013-December 2014). The American Center-Faint and Fall Clinic is run solely by a nurse practitioner, assisted by online faint-decision software and consultancy of a faint specialist through video-conferencing. Results Five hundred and twenty-eight consecutive patients were seen at the University of Wisconsin Hospital and Clinics-Faint and Fall Clinic and 68 patients at the American Center-Faint and Fall Clinic. The patients' clinical characteristics were similar except for a lower age in the American Center patients (45 ± 18 vs 51 ± 22, p = 0.03). Overall, a diagnosis was made within 45 days in 70% (95% confidence interval 66-74%) of the University of Wisconsin Hospital and Clinics patients and 69% (95% confidence interval 58-80%) of the American Center patients, ( p = 0.9). A mean of 3.0 ± 1.6 tests per patient was used in the University of Wisconsin Hospital and Clinics group compared to 1.5 ± 0.8 tests per patient in the American Center group, p = 0.001. Over the six-month study period, the total revenue at the American Center was US$152,597 (contribution margin of US$122,393 plus professional revenue of US$30,204). The total cost of the nurse practitioner including benefits was US$66,662 ((US$98,466 salary/year + 35.4% benefits)/2). Total revenue minus expenses resulted in a net profit of US$85,935. Discussion A nurse practitioner-run outreach syncope-clinic equipped with online faint-decision software and consultancy of a faint specialist through vedio-conferencing is feasible and financially self-sustainable. It allows the dissemination of standardized high-quality syncope care to patients who have no immediate access to a tertiary teaching hospital.

Benefit of dual-chamber pacing with Closed Loop Stimulation in tilt-induced cardio-inhibitory reflex syncope (BIOSync trial): study protocol for a randomized controlled trial.

BACKGROUND: The efficacy of dual-chamber cardiac pacing in neuro-mediated reflex syncope with a cardio-inhibitory response to the Tilt-Table test (TT) has not been definitively assessed so far. The lack of reproducibility of results from previous studies may be partially explained by discrepancies in subject selection and some weaknesses in design and methods. The European Society of Cardiology (ESC) has set a class IIb indication to pacemaker implantation in this population recommending further research. METHODS/DESIGN: The BIOSync study is a multicenter, patient- and outcome-assessor-blind, randomized, parallel-arm, placebo-controlled trial with the objective of assessing the clinical benefit of cardiac pacing in patients with frequently recurrent reflex syncope, suspected (but not proven) to be triggered by asystolic pauses as showing a VASIS 2B response to the TT (>3-s pause regardless of blood pressure drop). The primary and secondary endpoints are time to first post-implantation recurrence of syncope or the combination of pre-syncope or syncope, respectively. One hundred and twenty-eight consenting patients will be 1:1 randomized to dual-chamber cardiac pacing 'on' or 'off' after pacemaker implantation, and followed up until the first adjudicated primary endpoint event for a maximum of 2 years. The so-called Closed Loop Stimulation function on top of dual-chamber pacing is the pacing mode selected in the study active arm. Participating patients are asked to self-report syncopal symptoms at least every 3 months with self-administered questionnaires addressed to an independent Adjudication Committee. Patients and members of the Adjudicating Committee are blinded to randomization. The study is designed to detect a 40% relative reduction in the 2-year incidence of syncopal recurrences with 80% statistical power. DISCUSSION: The BIOSync study is designed to definitively assess the benefit of pacing against placebo in reflex syncope patients with a cardio-inhibitory response to the TT. The study will also provide important information on the efficiency of the TT in appropriately selecting reflex syncope patients for cardiac pacing. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02324920 (27 October 2016, date last accessed).

Clinical Characteristics and Outcome of Patients with Situational Syncope Compared to Patients with Vasovagal Syncope.

BACKGROUNDS: The purpose of the study was to assess the clinical outcome of patients with situational syncope (SS) compared to patients with vasovagal syncope (VVS). METHODS: We assessed the prevalence, patients' characteristics, and outcome of consecutive patients with SS and VVS who presented to the Faint and Fall Clinic (University of Wisconsin) between January 2013 and December 2015. RESULTS: SS was found in 55/1,401 (4.0%) syncope patients with follow-up data available in 47 patients: defecation (n = 16), micturition (n = 15), cough (n = 10), swallow (n = 3), laughter (n = 1), sneeze (n = 1), and cough plus laughter (n = 1). Over the same time period, 252/1,401 patients (18%) were diagnosed with VVS with follow-up data available in 171 patients. Compared with VVS patients, SS patients were older, more likely to be male, had a higher prevalence of hypertension, had an absence of prodromes, and experienced more injuries at the time of syncope (P = 0.01 for all). During a mean follow-up duration of 15.4 ± 9.1 months, syncope recurred in 5/47 (10.6%) patients with SS and 16/171 (9.4%) patients with VVS. The recurrence rates at 1 year and 2 years were 20% (95% SE ± 13) and 40% (95% SE ± 20) for the SS group, and 23% (95% SE ± 13) and 43% (95% SE ± 20) for the VVS group (P = 0.6). No patient died. CONCLUSIONS: We have shown in a large cohort of consecutive patients with syncope that SS is a relatively infrequent form of reflex syncope with different clinical characteristics but similar recurrence rate to VVS.

Long-Term Outcome of Patients with Bifascicular Block and Unexplained Syncope Following Cardiac Pacing.

BACKGROUND: According to the ACC/AHA/HRS guidelines, cardiac pacing is reasonable in patients with bifascicular block (BF-B) and syncope when other causes have been excluded. The purpose of this study was to assess the long-term outcome of patients with BF-B and unexplained syncope following cardiac pacing. METHODS AND RESULTS: Between 2009 and 2015, we identified 43 consecutive patients (mean age of 78 ± 12 years, 64% males) who presented with syncope and BF-B and had received a pacemaker (PM). During a mean follow-up period of 31 ± 21 months, syncope recurred in seven patients (16%): 7% (95% standard error [SE] ± 3%) at 1 year and 18% (95% SE ± 7%) at 5 years. At univariable analysis, the only predictor of syncope recurrence was empiric pacing (P = 0.03). There were no syncope recurrences in the 12 patients who received a PM following a positive electrophysiological study (EPS) and the five patients with documentation of paroxysmal atrioventricular block (AVB) during cardiac monitoring (insertable loop recorder [ILR]), (EPS/ILR Group, n = 17) compared to seven of 26 (27%) patients who received empiric pacing (Empiric Group, n = 26; P = 0.02). Progression to high-degree AVB was documented during follow-up in 16 (37%) patients: nine of 17 (53%) patients in the EPS/ILR Group and seven of 26 (27%) patients in the Empiric Group (P = 0.11). There were no injuries reported during ILR monitoring. CONCLUSIONS: We have shown that syncope recurs not infrequently in patients with BF-B who received pacing for syncope. Nearly one in four patients who had empiric pacing suffered syncope recurrence compared to no recurrences in patients who received a PM following a positive EPS or documentation of transient AVB.