Malcolm Kirk

Role of the transverse-axial tubule system in generating calcium sparks and calcium transients in rat atrial myocytes.

Cardiac atrial cells lack a regular system of transverse tubules like that in cardiac ventricular cells. Nevertheless, many atrial cells do possess an irregular internal transverse‐axial tubular system (TATS). To investigate the possible role of the TATS in excitation‐contraction coupling in atrial myocytes, we visualized the TATS (labelled with the fluorescent indicator, Di‐8‐ANEPPS) simultaneously with Ca2+ transients and/or Ca2+ sparks (fluo‐4). In confocal transverse linescan images of field‐stimulated cells, whole‐cell Ca2+ transients had two morphologies: ‘U‐shaped’ transients and irregular or ‘W‐shaped’ transients with a varying number of points of origin of the Ca2+ transient. About half (54 %, n=289 cells, 13 animals) of the cells had a TATS. Cells with TATS had a larger mean diameter (13.2 ± 2.8 μm) than cells without TATS (11.7 ± 2.0 μm) and were more common in the left atrium (n= 206 cells; left atrium: 76 with TATS, 30 without TATS; right atrium: 42 with TATS, 58 without TATS). Simultaneous measurement of Ca2+ sparks and sarcolemmal structures showed that cells without TATS had U‐shaped transients that started at the cell periphery, and cells with TATS had W‐shaped transients that began simultaneously at the cell periphery and the TATS. Most (82 out of 102 from 31 cells) ‘spontaneous’ (non‐depolarized) Ca2+ sparks occurred within 1 μm of a sarcolemmal structure (cell periphery or TATS), and 33 % occurred within 1 pixel (0.125 μm). We conclude that the presence of a sarcolemmal membrane either at the cell periphery or in the TATS in close apposition to the sarcoplasmic reticulum is required for the initiation of an evoked Ca2+ transient and for spontaneous Ca2+ sparks.

Enhanced detection of arrhythmia vulnerability using T wave alternans, left ventricular ejection fraction, and programmed ventricular stimulation: a prospective study in subjects with chronic ischemic heart disease.

Introduction: In previous studies, the prognostic value of T wave alternans (TWA) was similar to that of programmed ventricular stimulation (PVS). However, presently it is unclear if TWA and PVS identify the same patients or provide complementary risk stratification information. In addition, the effects of left ventricular ejection fraction (LVEF) on the prognostic value of TWA are unknown. The aim of this study was to determine if combined assessment of TWA, LVEF, and PVS improves arrhythmia risk stratification.

Exercise is Superior to Pacing for T Wave Alternans Measurement in Subjects with Chronic Coronary Artery Disease and Left Ventricular Dysfunction

Exercise vs Pacing for TWA Measurement. Introduction: T wave alternans (TWA) is a heart rate‐dependent marker of vulnerability to ventricular arrhythmias. Atrial pacing and exercise both are used as provocative stimuli to elicit TWA. However, the prognostic value of the two testing methods has not been compared. The aim of this prospective study was to compare the prognostic value of TWA measured during bicycle exercise and atrial pacing in a large cohort of high‐risk patients with ischemic heart disease and left ventricular dysfunction.

Influence of QRS duration on the prognostic value of T wave alternans.

T Wave Alternans and QRS Duration. Introduction: T wave alternans (TWA) is a promising new noninvasive marker of arrhythmia vulnerability that quantifies beat‐to‐beat changes in ventricular repolarization. Secondary repolarization abnormalities are common in subjects with wide QRS complexes. However, the relationship between TWA and QRS prolongation has not been evaluated. The goal of this study was to determine if QRS prolongation influences the prevalence or prognostic value of TWA.

Temporal decline in defibrillation thresholds with an active pectoral lead system

OBJECTIVES The objective of this study was to characterize temporal changes in defibrillation thresholds (DFTs) after implantation with an active pectoral, dual-coil transvenous lead system. BACKGROUND Ventricular DFTs rise over time when monophasic waveforms are used with non-thoracotomy lead systems. This effect is attenuated when biphasic waveforms are used with transvenous lead systems; however, significant increases in DFT still occur in a minority of patients. The long-term stability of DFTs with contemporary active pectoral lead systems is unknown. METHODS This study was a prospective assessment of temporal changes in DFT using a uniform testing algorithm, shock polarity and dual-coil active pectoral lead system. Thresholds were measured at implantation, before discharge and at long-term follow-up (70 +/- 40 weeks) in 50 patients. RESULTS The DFTs were 9.2 +/- 5.4 J at implantation, 8.3 +/- 5.8 J before discharge and 6.9 +/- 3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long-term follow-up vs. at implantation or before discharge). The effect was most marked in a prespecified subgroup with high implant DFTs (> or =15 J). No patient developed an inadequate safety margin (< 9 J) during follow-up. CONCLUSIONS The DFTs declined significantly after implantation with an active pectoral, dual-coil transvenous lead system, and no clinically significant increases in DFT were observed. Therefore, routine defibrillation testing may not be required during the first two years after implantation with this lead system, in the absence of a change in the cardiac substrate or treatment with antiarrhythmic drugs.

Comparison of the effects of active left and right pectoral pulse generators on defibrillation efficacy

P placement of implantable cardioverter-defibrillator (ICD) pulse generators is now routine because of the steady decrease in pulse generator size. With left pectoral positioning, the generator shell can be incorporated into the shocking pathway as an “active can,” resulting in a lowering of defibrillation thresholds (DFTs). Uniformly low DFTs can be achieved with the combination of biphasic waveforms, active cans, and advanced lead design, particularly dual-coil leads. Despite the ubiquitous use of active cans, the mechanism by which they reduce defibrillation energy requirements is controversial. Although some studies have suggested that the reduction in energy requirements is due to optimization of the shock vector, directing more current through the left ventricle, other studies indicate that reduction of shock impedance is more important. An active can in a right pectoral position, however, would be expected to reduce impedance but possibly worsen the current vector. A case report and 2 retrospective series have demonstrated that use of a right pectoral active can is feasible. The effect of such a shocking configuration on defibrillation efficacy has not been evaluated directly. The present study is a prospective comparison of the effect of an active can on DFTs in the right and left pectoral position. This was a study of 126 patients undergoing ICD implantation for standard clinical indications. Each patient gave written informed consent and the institutional review board of the University of Maryland approved this study. Right-sided implants were performed in 25 patients because of contraindications to left pectoral implantation. These contraindications included 7 patients with abandoned left-sided lead systems due to erosion, ICD incompatibility or infection, 5 patients with explanted left-sided lead systems for similar indications, 5 patients with left arm arteriovenous shunts or fistulas for hemodialysis, and 2 patients with left-sided pacemakers. Other indications for right pectoral placement included upgrading of a preexisting right-sided permanent pacemaker, left superior vena cava thrombosis, left mastectomy, and previous left arm vein harvest for coronary artery bypass surgery. These patients were compared with 101 patients who had routine left pectoral ICD implants performed over the same time period. All patients received an integrated dual-coil lead system. This was an Endotak lead (Guidant Corp., St. Paul, Minnesota) in 120 subjects including 20 with right-sided implants and a Sprint lead (Medtronic Inc., Minneapolis, Minnesota) in the remaining 6 patients. The lead was introduced via the axillary, cephalic, or subclavian vein, and the tip positioned in the right ventricular apex so that the distal end of the proximal coil was near the right atrium/superior vena cava junction. After lead implantation, a prepectoral pocket was created for the pulse generator emulator. All testing was performed using conscious sedation with midazolam and fentanyl. Two shocking configurations were tested in each patient in random order: (1) with the 2 coil transvenous lead only, called “lead alone”; and (2) with a pulse generator emulator (model 6967, Guidant Corp.) in the prepectoral pocket, connected electrically to the proximal transvenous coil, called “active can” configuration. The right ventricular coil was the cathode for the first phase of the biphasic shock in all testing. Testing was performed with an external defibrillator (ECD model 2815, Guidant Corp.), which delivers a 60%/50% tilt, biphasic waveform through a 150 F capacitance. Ventricular fibrillation was induced with high output ramp pacing through the defibrillator lead. The DFT was determined using a modified step-down protocol to first failure. Testing began at a 15-J delivered energy and decreased to 10, 8, 5, 3, and 1 J on subsequent trials. If the 15-J shock failed, the first shock energy was increased in 5-J steps on subsequent trials until defibrillation was successful. At least 3 minutes were allowed between shocks for full hemodynamic recovery. The DFT was defined as the lowest first shock energy that achieved successful defibrillation. After a failed shock, a higher energy rescue shock was delivered immediately. The patients were grouped on the basis of pectoral implantation position, left or right. Proportions were analyzed by Fisher’s exact test. Continuous data were expressed as mean values SD and analyzed by t tests. Paired t tests were used for comparing the effect of electrode configuration on defibrillation parameters. A p value 0.05 was considered significant. From the Department of Medicine, Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland. Dr. Gold’s address is: Division of Cardiology, N3W77, University of Maryland, 22 South Greene Street, Baltimore, Maryland 21201. E-mail: Mgold@medicine.umaryland.edu. Manuscript received June 13, 2001; revised manuscript received and accepted August 6, 2001. TABLE 1 Clinical Characteristics of Patients with Leftand Right-Sided ICD Implants