Wayne O. Adkisson

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.

Presentation of synthetic peptide antigen encoded by the MAGE-1 gene by granulocyte/macrophage-colony-stimulating-factor-cultured macrophages from HLA-A1 melanoma patients

The recent identification of the sequences of the peptides derived from a number of human melanomaassociated antigens has presented opportunities for developing a specific-peptide-based vaccine in this form of cancer. Since antigen-presenting cells (APC) play a crucial role in the induction of the T-cell-mediated immune response, we examined whether or not ex vivo cultured APC, bearing the appropriate MHC restricting elements, when pulsed with a relevant melanoma-specific cytotoxic-T-lymphocyte(CTL)-determined peptide, can present the peptide to the CTL. Here we show that a population of cells, derived from the monocyte/macrophage lineage from peripheral blood and grown in granulocyte/macrophage-colony-stimulating factor, exhibit many essential characteristics of “professional” APC (dendritic-type morphology with a proportion of the population, the B7 molecule, and high levels of MHC class I and class II molecules, CD11b and CD54 molecules) and are capable of efficiently presenting the nonapeptide, EADPTGHSY, encoded by the melanoma antigen MAGE-1 gene, to the MAGE-1-specific CTL clone, 82/30. These results suggest that this type of autologous ex vivo cultured population of professional APC, when pulsed with the relevant-CTL-determined peptide, can serve as a novel type of candidate vaccine for active specific immunization against HLAA1-positive patients with melanoma expressing the MAGE-1 antigen.

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.

Measurement of adenylylcyclase activity in the AV nodal region of the canine heart : Evidence for inhibition by adenosine and acetylcholine

Although it is essential to cardiac conduction, little is known about the biochemistry underlying postreceptor adrenergic, cholinergic and purinergic processes in the AV node. To study these mechanisms, we adapted a new and highly sensitive fluorometric assay for cyclic adenosine monophosphate (AMP) to characterize regional adenylylcyclase activity (cyclic AMP production in pmol/min/mg of protein) in membrane preparations made from 20-50 pieces of freeze-dried, 20-microm thick, microdissected samples of tissue from canine right atrium, the AV nodal region, and left ventricle. Basal and NaF-stimulated adenylylcyclase activity (mean +/- SEM, n = 6) were 7.2 +/- 0.4 and 72.4 +/- 7.5 in atrial, 15.6 +/- 1.3 and 58.8 +/- 4.7 in AV nodal, and 6.4 +/- 0.9 and 66.7 +/- 5.0 in ventricular tissues, respectively. Isoproterenol (10(-7)-10(-4) M) increased adenylylcyclase activity in a dose-dependent fashion in three different regions. The isoproterenol (10(-6) M)-stimulated adenylylcyclase activity (n = 6) was 14.4 +/- 1.3 in atrial, 21.9 +/- 1.6 in AV nodal and 13.4 +/- 1.4 in ventricular tissues. Adenosine (10(-3) M) and carbachol (10(-5) M) inhibited isoproterenol (10(-6) M)-stimulated adenylylcyclase activity to 10.1 +/- 1.1, 12.9 +/- 1.3 in atrial, 15.1 +/- 1.6, 15.5 +/- 1.2 in AV nodal, and 7.5 +/- 0.7, 11.9 +/- 1.2 in ventricular tissues, respectively. The results demonstrate that there are regional differences in adenylylcyclase activity under basal conditions and after adrenergic, purinergic, and cholinergic stimulation in the heart. Unlike adenosine, the inhibitory effects of cholinergic stimulation appear to be more specific for the AV node.

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.

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

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.

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.

Comparison of Right Atrial and Peripheral Procainamide Infusion Levels in Patients with Spontaneous or Induced Atrial Fibrillation

As part of a new effort to develop an implantable drug infusion pacing system to treat atrial fibrillation, this study examined the effects of rapid intracardiac procainamide infusion in humans with pacing‐induced atrial fibrillation. Twenty patients with atrial fibrillation for >5 minutes during an EP study received 500mg of procainamide either via a peripheral venotis infusion (n=5) or directly in the right atrium (n=15). Peak coronary simis and femoral vein procainamide blood levels (mean ± SEM) during 10, 5, and 3.3 minute central infusions were 17.0 ± 4.1, 25.1 ± 4.5, 45.6 ± 5.1 and 11.3 ± 3.2, 17.1 ± 6.4, 18.7 ± 5.0, respectively. In contrast, peak coronary sinus and femoral procainamide levels following the 5 minute intravenous infusion were 17.7 ± 5.1 and 9.3 ± 2.1. Changes in QT, QTc, QRS, and RI intervals were similar at each infiision rate. Systolic blood pressures (BP) decreased more with higher procainamide infusion rates but similar when comparing intravenous versus central drug administration at the same rate. The mean ± SEM decreases in blood pressure with the 10, 5, and 3.3 min procainamide infusions were 12f5, 20f11, and 39f14, respectively. Conversion to sinus rhythm was not a primary endpoint given the often transient nature of acute atrial fibrillation in this setting. We conclude that significantly higher femoral vein and coronary sinus procainamide levels can be achieved by central rather than peripheral drug infusion. These data support that concept that rapid central infitsion of anti‐arrhythmic therapy can result in high intracardiac levels of antifibrillatory agents for the treatment of paroxysmal atrial fibrillation.

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

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.

Swallow (Deglutition) Syncope: An Evaluation of Swallowing-Induced Heart Rate and Hemodynamic Changes in Affected Patients and Control Subjects: KOHNO et al.

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.