Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association.

Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. Conclusions Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.

Neurohormones in the Pathophysiology of Vasovagal Syncope in Adults.

Vasovagal syncope (VVS) is the most common cause of syncope across all age groups. Nonetheless, despite its clinical importance and considerable research effort over many years, the pathophysiology of VVS remains incompletely understood. In this regard, numerous studies have been undertaken in an attempt to improve insight into the evolution of VVS episodes and many of these studies have examined neurohormonal changes that occur during the progression of VVS events primarily using the head-up tilt table testing model. In this regard, the most consistent finding is a marked increase in epinephrine (Epi) spillover into the circulation beginning at an early stage as VVS evolves. Reported alterations of circulating norepinephrine (NE), on the other hand, have been more variable. Plasma concentrations of other vasoactive agents have been reported to exhibit more variable changes during a VVS event, and for the most part change somewhat later, but in some instances the changes are quite marked. The neurohormones that have drawn the most attention include arginine vasopressin [AVP], adrenomedullin, to a lesser extent brain and atrial natriuretic peptides (BNP, ANP), opioids, endothelin-1 (ET-1) and serotonin. However, whether some or all of these diverse agents contribute directly to VVS pathophysiology or are principally a compensatory response to an evolving hemodynamic crisis is as yet uncertain. The goal of this communication is to summarize key reported neurohumoral findings in VVS, and endeavor to ascertain how they may contribute to observed hemodynamic alterations during VVS.

Swallow (deglutition) syncope: An evaluation of swallowing-induced heart rate and hemodynamic changes in affected patients and control subjects.

BACKGROUND: Syncope triggered by swallowing is a well-known but uncommon condition that has been the focus of case reports but is otherwise largely unstudied. To better understand swallow syncope we examined heart rate (HR) and blood pressure (BP) changes during swallowing in clinically suspected swallow syncope patients and asymptomatic control subjects. METHODS: The study population comprised four individuals with a history suggesting swallow syncope (three men, 53 ± 14.9 years) and 15 (nine men, 46 ± 17.1 years, P = NS vs patients) asymptomatic volunteer control subjects. Studies in all individuals comprised noninvasive beat-to-beat HR and BP measurement during swallowing 150 mL of cold liquid while standing. Additional tests in swallow syncope patients included: active standing, Valsalva maneuver, carotid sinus massage (CSM), and head-up tilt (HUT). RESULTS: Swallowing resulted in a greater decrease of both HR (-22 ± 22.1 vs -3 ± 11.7 beats/minute [bpm]; P = 0.045) and BP (-22 ± 17.4 vs - 2 ± 11.8; P = 0.036) in swallow syncope patients than in controls. Further, in swallow syncope patients the time to lowest HR and BP differed (9 ± 5.5 vs 19 ± 7.2 seconds; P = 0.02), suggesting that both cardioinhibitory (CI) and vasodepressor (VD) mechanisms are present but operate independently. Other autonomic studies were normal in swallow syncope patients except for CSM pause more than 3 seconds in two patients. CONCLUSION: Swallow syncope is associated with transient and temporally independent CI and VD features, consistent with reflex syncope. Potentially, a swallowing test during autonomic evaluation may be useful to unmask relative magnitudes of CI and VD responses, thereby facilitating treatment strategy decisions.

Tilt table testing for syncope and collapse.

Head-up tilt (HUT) has long been used to examine heart rate and blood pressure adaptation to changes in position. During such studies, incidental observations noted that some test subjects experienced total or near-total transient loss of consciousness and that, in some cases, hypotension was associated with unexpected marked bradycardia compatible with a vasovagal syncope (VVS) reaction. The first report of HUT as a clinical tool to confirm a diagnosis of suspected VVS was published in 1966, and led to the concept of using HUT as a diagnostic tool for VVS. Subsequently, HUT testing, either drug-free or, if necessary, with pharmacological provocation (usually nitroglycerin) has proven to be a useful and safe modality for identifying susceptibility to VVS. In this regard, it is recognized that VVS is best diagnosed by careful history taking. Unfortunately, the history may be non-diagnostic; HUT may be helpful in such cases. However, the interpretation of HUT requires care and experience; in particular, the outcome must be consistent with the patient's clinical presentation. The reproduction of patient symptoms may not only provide a diagnosis, but also offer some comfort to the patient and family in that the medical team has documented the basis of symptoms and are thereby positioned to address therapy.

Trends of hospitalizations for syncope/collapse in the United States from 2004 to 2013-An analysis of national inpatient sample.

INTRODUCTION: Syncope/collapse is a common reason for emergency department visits, and approximately 30-40% of these individuals are hospitalized. We examined changes in hospitalization rates, in-hospital mortality, and cost of syncope/collapse-related hospital care in the United States from 2004 to 2013. METHODS: We used the US Nationwide Inpatient Sample (NIS) from 2004 to 2013 to identify syncope/collapse-related hospitalizations using ICD-9, code 780.2, as the principal discharge diagnosis. Data are presented as mean ± SEM. RESULTS: From 2004 to 2013, there was a 42% reduction in hospitalizations with a principal discharge diagnosis of syncope/collapse from 54,259 (national estimate 253,591) in 2004 to 31,427 (national estimate 156,820) in 2013 (P < 0.0001). The mean length of hospital stays decreased (2.88 ± 0.04 days in 2004 vs. 2.54 ± 0.02 in 2013; P < 0.0001), while in-hospital mortality did not change (0.28% in 2004 vs. 0.18% in 2013; P  =  0.12). However, mean charges (inflation adjusted) for syncope/collapse-related hospitalization increased by 43.6% from $17,514 in 2004 to $25,160 in 2013 (P < 0.0001). The rates of implantation of permanent pacemakers and implantable cardioverter defibrillator remained low during these hospitalizations, and decreased over time (P for both < 0.0001). CONCLUSIONS: Hospitalization rates for syncope/collapse have decreased significantly in the US from 2004 to 2013. Despite a modest reduction in length of stay, the cost of syncope/collapse-related hospital care has increased.

Ambulatory diagnostic ECG monitoring for syncope and collapse: An assessment of clinical practice in the United States.

INTRODUCTION: Diagnostic ambulatory electrocardiogram (AECG) monitoring is widely used for evaluating syncope and collapse, and practice guidelines provide recommendations regarding optimal AECG device selection. However, whether physicians utilize AECGs in accordance with the pertinent guidelines is unclear. This study assessed utilization of AECG monitoring systems for syncope and collapse diagnosis by physicians in the United States. METHODS AND RESULTS: A quantitative survey was undertaken of physicians comprising multiple specialties (emergency department, n = 35; primary care, n = 35; hospitalists, n = 30; neurologists, n = 30; nonimplanting, n = 34, and implanting-cardiologists, n = 35). Depending on specialty, respondents reported that neural-reflex and orthostatic causes accounted for 17-23%, cardiac causes for 12-20%, and "neurological causes" (specifically psychogenic pseudo-syncope/pseudo-seizures and acute cerebrovascular conditions) for 7-12% of their syncope/collapse cases. The choice of AECG technology varied by specialty. Thus, despite patients having daily symptoms, 25% of respondents chose an AECG technology other than a Holter-type monitor. Conversely, when monitoring for infrequent events (e.g., less than monthly), 12-18% indicated that they would choose a 24- to 48-hour Holter, 20-34% would choose either a conventional event recorder or a mobile cardiac telemetry system, and only 53-65% would select an insertable cardiac monitor. CONCLUSIONS: In evaluation of syncope/collapse, most U.S. clinicians across specialties use AECGs appropriately, but in a substantial minority there remains discordance between choice of AECG technology and guideline-based recommendations.

Syncope and the risk of sudden cardiac death: Evaluation, management, and prevention.

Syncope is a clinical syndrome defined as a relatively brief self-limited transient loss of consciousness (TLOC) caused by a period of inadequate cerebral nutrient flow. Most often the trigger is an abrupt drop of systemic blood pressure. True syncope must be distinguished from other common non-syncope conditions in which real or apparent TLOC may occur such as seizures, concussions, or accidental falls. The causes of syncope are diverse, but in most instances, are relatively benign (e.g., reflex and orthostatic faints) with the main risks being accidents and/or injury. However, in some instances, syncope may be due to more worrisome conditions (particularly those associated with cardiac structural disease or channelopathies); in such circumstances, syncope may be an indicator of increased morbidity and mortality risk, including sudden cardiac death (SCD). Establishing an accurate basis for the etiology of syncope is crucial in order to initiate effective therapy. In this review, we focus primarily on the causes of syncope that are associated with increased SCD risk (i.e., sudden arrhythmic cardiac death), and the management of these patients. In addition, we discuss the limitations of our understanding of SCD in relation to syncope, and propose future studies that may ultimately address how to improve outcomes of syncope patients and reduce SCD risk.

Pathophysiology of reflex syncope: A review.

In this correspondence, the pathophysiology of reflex syncope (vasovagal syncope, carotid sinus syndrome, and situational syncope) is reviewed, including clarification of the nomenclature.

Usefulness of Atrial Fibrillation as a Marker for Adverse Cardiovascular Outcomes in Both Primary and Secondary Prevention in Patients With Implantable Cardioverter-Defibrillators.

Whether the risk factors for cardiovascular (CV) outcomes are different in primary versus secondary prevention implantable cardioverter-defibrillator (ICD) patients is unclear. We sought to identify predictors of CV outcomes in ICD recipients for primary (G1) versus secondary prevention (G2). Consecutive patients who had ICD implanted during August 2005 to December 2009 were included. The primary outcome was a composite of appropriate shock, acute coronary syndrome, ischemic stroke, coronary revascularization, heart failure exacerbation, CV hospitalization, or all-cause death. We used Cox proportional hazards model and a stepwise selection method to fit the most parsimonious model to predict the primary outcome in all patients and separately for G1 and G2 patients. We followed 223 (184 G1 and 39 G2, mean age 61 years) patients through December 31, 2012; 141 (63.2%) developed the primary outcome. In all patients, atrial fibrillation (AF; hazard ratio 6.72, 95% CI 4.20 to 10.75; p <0.001), use of antiarrhythmic drug (1.55, 1.02 to 2.36; p = 0.04), and lower estimated glomerular filtration rate (0.99, 0.98 to 0.997; p = 0.01) were associated with increased risk of the primary outcome; the attributable risks were 21.6%, 16.0%, and 15.9%, respectively. In G1, AF, hypertension, and lower estimated glomerular filtration rate were associated with increased risk, whereas in G2, AF, use of antiarrhythmic drug, and nonischemic cardiomyopathy were associated with increased risk. In conclusion, although risk factors are different for primary and secondary prevention patients, AF is a strong and consistent risk factor for adverse outcomes in both populations.

Premature ventricular contractions: Reassure or refer?

When patients present with palpitations, the primary care physician can perform the initial evaluation and treatment for premature ventricular contractions (PVCs). Many patients need only reassurance and do not need to see a cardiologist.

Blunted Chronotropic Response to Hypotension in Cough Syncope.

OBJECTIVES: This study compared hemodynamic and chronotropic responses to cough in cough syncope (CS) patients to those in control subjects. BACKGROUND: Cough syncope is an uncommon form of situational fainting variously attributed to both reflex and mechanical causes. We hypothesized that if baroreflex responses contribute to CS, post-cough hypotension should be associated with cardioinhibition comparable to that observed in other reflex faints. METHODS: The study population consisted of 8 CS patients (group 1), 21 patients with vasovagal syncope (group 2), and 6 patients with nonvertiginous "lightheadedness" (group 3). Testing with patients seated included volitional coughing that achieved a transient blood pressure (BP) of ≥200 mm Hg. Beat-to-beat blood pressure (systolic blood pressure [SBP]) before cough, minimum cough-induced SBP and heart rate (HR) (beats/min) after cough, and HR change during cough-induced hypotension were recorded, along with SBP recovery time from SBP nadir after cough. RESULTS: Compared to controls, cough-induced SBP drop was greater in CS patients (CS patients: -48 ± 13.1 mm Hg vs. -29 ± 11.2 mm Hg for group 2 controls; p = 0.005; or -25 ± 10 mm Hg in group 3 controls; p = 0.02), and recovery time was longer (CS: 46 ± 19 s vs. 11 ± 3.6 s in group 1 controls; p = 0.002; or 12 ± 5 s in group 3 controls; p = 0.01). Furthermore, despite greater induced hypotension, post-cough chronotropic response was less in CS patients (+15% above baseline rate) than in either group 2 (+31% above baseline rate; p < 0.001) or group 3 (+28%; p = 0.01) controls. CONCLUSIONS: In CS patients, post-cough chronotropic response is blunted compared to that in controls despite greater cough-induced hypotension favoring baroreflex cardioinhibition contribution to the pathophysiology of cough syncope.

Syncope due to Autonomic Dysfunction: Diagnosis and Management.

Syncope is one of several disorders that cause transient loss of consciousness. Cerebral hypoperfusion is the proximate cause of syncope. Transient or fixed autonomic nervous system dysfunction is a major contributor in many causes. A structured approach to the evaluation of syncope allows for more effective therapy.

Catheter ablation for long-standing persistent atrial fibrillation in patients who have failed electrical cardioversion.

Ablation outcomes in 22 consecutive long-standing persistent atrial fibrillation (LPAF) patients with failed direct current cardioversion (DCCV; group 1) were compared with findings in 22 consecutive LPAF patients who had successful DCCV (control 1) and 22 consecutive patients with paroxysmal atrial fibrillation (AF; control 2). All patients underwent a stepwise progressive ablation protocol (pulmonary vein isolation, ablation of complex fractionated atrial electrogram, and repeat ablation of any induced atrial tachycardias). Over 18-month follow-up, 59 % of group 1 patients remained in sinus rhythm without recurrent AF, compared to 64 % and 77 % in controls 1 and 2, respectively. The procedure time was longer in LPAF with a higher procedure complication risk in these 44 LPAF patients (5 % vs. 0 %) than in patients with paroxysmal AF. Our data suggest that catheter ablation provides a practical treatment option with moderate efficacy for restoring sinus rhythm in LPAF patients after failed DCCV.

Approach to the patient with syncope: venues, presentations, diagnoses.

Syncope is a frequent cause for presentation to emergency departments and urgent-care clinics. The physician should establish a confident causal diagnosis, assess prognostic implications, and provide appropriate advice to prevent recurrences. An organized approach is needed to the assessment of the patient with syncope, including a careful initial examination as well as application of specialized syncope evaluation units and structured questionnaires for history taking. The initial patient evaluation, particularly a detailed medical history, is the key to identifying the most likely diagnosis. Based on these findings, subsequent diagnostic tests can be chosen to confirm the clinical suspicion.

Age-dependence of relative change in circulating epinephrine and norepinephrine concentrations during tilt-induced vasovagal syncope.

BACKGROUND: Although vasovagal syncope (VVS) is preceded by a surge of circulating catecholamines (epinephrine [Epi] and norepinephrine [NE]) of adrenal/renal and synaptic origin, prevention of VVS with ß-adrenergic blockade has been ineffective except in "older" VVS patients. OBJECTIVE: We hypothesized that age-related differences of ß-blocker effect may be due in part to differences in the relative magnitudes of Epi and NE release during an evolving faint, specifically, greater Epi/NE ratio in younger fainters compared to older patients. To assess this hypothesis, we measured changes in Epi/NE ratios in younger (<40 years) vs older (≥40 years) patients during head-up tilt-table test-induced VVS. METHODS: The study comprised 29 patients (12 patients ≥40 years [mean 56 ± 10.7 years] and 17 patients <40 years mean 25 ± 5.7 years]) with recurrent suspected VVS in whom 70° head-up tilt testing reproduced symptoms. Arterial Epi and NE concentrations were measured at baseline (supine), 2 minutes of head-up tilt, and syncope. RESULTS: Baseline Epi and NE concentrations and the Epi/NE ratio did not differ in younger and older groups (Epi: 90 ± 65 pg/mL vs 70 ± 32 pg/mL; NE: 226 ± 122 pg/mL vs 244 ± 183 pg/mL). However, Epi/NE ratio increased to a greater extent in younger fainters during head-up tilt and tended to be greater in younger patients at both 2 minutes (<40: 1.02 ± 1.29 vs ≥40: 0.40 ± 0.27, P = .11) and at symptoms (<40: 2.6 ± 1.26 vs ≥40: 1.6 ± 0.71, P = .03). At symptoms, Epi/NE ratio ≥2.5 was observed in 9 of 17 younger patients vs 1 of 12 older patients (P = .02). CONCLUSION: Epi/NE ratios tend to be greater in younger fainters, a finding that may account in part for the observation that ß-blocker therapy is less effective in reducing VVS susceptibility in younger individuals.

Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results.

BACKGROUND: Successful antitachycardia pacing (ATP) terminates ventricular tachycardia (VT) up to 250 bpm without the need for painful shocks in implantable cardioverter-defibrillator (ICD) patients. Fast VT (FVT) >200 bpm is often treated by shock because of safety concerns, however. This prospective, randomized, multicenter trial compares the safety and utility of empirical ATP with shocks for FVT in a broad ICD population. METHODS AND RESULTS: We randomized 634 ICD patients to 2 arms-standardized empirical ATP (n=313) or shock (n=321)-for initial therapy of spontaneous FVT. ICDs were programmed to detect FVT when 18 of 24 intervals were 188 to 250 bpm and 0 of the last 8 intervals were >250 bpm. Initial FVT therapy was ATP (8 pulses, 88% of FVT cycle length) or shock at 10 J above the defibrillation threshold. Syncope and arrhythmic symptoms were collected through patient diaries and interviews. In 11+/-3 months of follow-up, 431 episodes of FVT occurred in 98 patients, representing 32% of ventricular tachyarrhythmias and 76% of those that would be detected as ventricular fibrillation and shocked with traditional ICD programming. ATP was effective in 229 of 284 episodes in the ATP arm (81%, 72% adjusted). Acceleration, episode duration, syncope, and sudden death were similar between arms. Quality of life, measured with the SF-36, improved in patients with FVT in both arms but more so in the ATP arm. CONCLUSIONS: Compared with shocks, empirical ATP for FVT is highly effective, is equally safe, and improves quality of life. ATP may be the preferred FVT therapy in most ICD patients.