Integrated microscopy techniques for comprehensive pathology evaluation of an implantable left atrial pressure sensor.

The safety and efficacy of an implantable left atrial pressure (LAP) monitoring system is being evaluated in a clinical trial setting. Because the number of available specimens from the clinical trial for histopathology analysis is limited, it is beneficial to maximize the usage of each available specimen by relying on integrated microscopy techniques. The aim of this study is to demonstrate how a comprehensive pathology analysis of a single specimen may be reliably achieved using integrated microscopy techniques. Integrated microscopy techniques consisting of high-resolution gross digital photography followed by micro-computed tomography (micro-CT) scanning, low-vacuum scanning electron microscopy (LVSEM), and microground histology with special stains were applied to the same specimen. Integrated microscopy techniques were applied to eight human specimens. Micro-CT evaluation was beneficial for pinpointing the location and position of the device within the tissue, and for identifying any areas of interest or structural flaws that required additional examination. Usage of LVSEM was reliable in analyzing surface topography and cell type without destroying the integrity of the specimen. Following LVSEM, the specimen remained suitable for embedding in plastic and sectioning for light microscopy, using the positional data gathered from the micro-CT to intersect areas of interest in the slide. Finally, hematoxylin and eosin (H&E) and methylene blue staining was deployed on the slides with high-resolution results. The integration of multiple techniques on a single specimen maximized the usage of the limited number of available specimens from the clinical trial setting. Additionally, this integrated microscopic evaluation approach was found to have the added benefit of providing greater assurance of the derived conclusions because it was possible to cross-validate the results from multiple tests on the same specimen.

Radiofrequency ablation for common atrial flutter using an 8-mm tip catheter and up to 150 W.

The formation of bi-directional block in atrial flutter can be adversely affected by problems with the delivery of effective energy related to isthmus anatomy and contact. Higher energies can produce larger and more effective lesions. The optimum setting for power delivery using temperature controlled ablation has not been established, with the maximum reported being 100 W. This is a retrospective review of the first 50 new cases assessing the efficacy and safety of using temperature controlled (60-65 degrees C) flutter ablation with an 8mm tip electrode catheter and up to 150 W. All cases had either typical flutter alone (34%) or predominant flutter as the indication, no combined procedures were included. Acute procedural success was 94% and long-term success of 88%. Median number of ablations required was 11 (interquartile range 10-19), median procedure time 120 min (IQR 102-164), fluoroscopy time 22 min (IQR 17-36), radiation dose 17 Gy cm(2) (IQR 10-27), median number of lines 1 (IQR 1-2). Six patients achieved 150 W, but 42 achieved >100 W (median watts 142 W, IQR 104-147). Patients (12%) experienced an uncomplicated pop during the procedure. None experienced a significant complication. There were three late relapses. The setting of 150 W maximum delivered energy in temperature regulated ablation allowed higher energies (>100 W) to be delivered in most patients. This resulted in acute and long-term success rates that compare well with the literature but is associated with a 12% rate of pop. Subsequent to this series our 54th patient sustained a pop due to high energy ablation that resulted in perforation and tamponade, from which there was survival.

Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope.

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.

Baroreceptor denervation presenting as part of a vagal mononeuropathy.

A 48-year-old woman presented with a history of progressive cough, dysphonia, dysphagia, and postural symptoms. Subsequent neurological investigations were consistent with a bilateral vagal mononeuropathy, and neurosarcoidosis was diagnosed after scalene node biopsy. Autonomic investigations including microneurography, neurohormones, and heart rate variability demonstrated arterial and cardiopulmonary baroreflex failure. In addition, parasympathetic control of heart rate was absent and consistent with a bilateral, nonselective lesion in the proximal vagus.

Optimal cardiac pacing after heart transplantation.

The transplanted heart is characterized physiologically by autonomic denervation, chronotropic incompetence, intermittent episodes of allograft rejection, and frequently by diastolic dysfunction. Sinus node dysfunction resulting in bradycardia is common in the early postoperative period following standard orthotopic cardiac transplantation. Bradycardia tends to remit spontaneously but there are no factors that accurately identify patients who will need long-term pacing. Patients in whom bradycardia persists beyond the second postoperative week despite treatment with theophylline require permanent pacemaker implantation. It has been observed that chronotropic incompetence and diastolic dysfunction are important determinants of exercise capacity following heart transplantation. Pacing that restores chronotropic competence improves exercise capacity, confirming the importance of impaired heart rate response. As in other settings, pacing that preserves atrioventricular (AV) synchrony results in increased cardiac output. For these reasons when pacing is necessary we recommend the DDDR mode (AAIR if intact AV nodal conduction is present) so that the 30%-50% of patients who remain pacemaker-dependent long-term obtain maximal benefit from their transplant.

Neurohormonal response to head-up tilt and its role in vasovagal syncope.

In a controlled study, 26 patients with a history of recurrent syncope were found to have increased arginine vasopressin, corticotrophin, and atrial natriuretic factor levels after 5 minutes of 60 degrees head-up tilt, long before they became hypotensive. The exaggerated neurohormonal response in these patients may indicate a greater sensitivity to central hypovolemia which may predispose to vasovagal syncope, mediated by the vasodilatory effects of atrial natriuretic factor or the sensitization of mechanoreceptors by arginine vasopressin.