Resynchronization therapy for congestive heart failure

Opinion statement Ventricular contraction is achieved by the coordinated electrical activation of the ventricles through the action of the cardiac conduction system. In the presence of left bundle branch block (LBBB) or interventricular conduction delay (IVCD), the ventricular contraction pattern is desynchronized and the stroke volume is reduced as a consequence. In patients with congestive heart failure (CHF) due to systolic dysfunction, the presence of LBBB or IVCD further degrades ventricular function, contributing directly to the severity of their CHF symptoms. Cardiac resynchronization therapy (CRT) through biventricular pacing relieves CHF symptoms and improves functional status in patients with medically refractory heart failure due to left ventricular systolic dysfunction and LBBB or IVCD. The benefits of CRT are due to improvement in the ventricular activation sequence, resulting in a more coordinated and efficient ventricular contraction. In addition to symptomatic benefits, available data support the hypothesis that CRT alters the natural history of CHF in patients with intraventricular conduction delay.     

Magnetic guidance system for cardiac electrophysiology: a prospective trial of safety and efficacy in humans

OBJECTIVES: We evaluated in humans the safety and efficacy of a novel magnetic guidance system (MGS) for electrophysiological mapping, pacing, and ablation. BACKGROUND: Catheter ablation of atrial fibrillation and other complex arrhythmias requires precise catheter manipulation and stabilization. We have shown in animals that the MGS can precisely manipulate a mapping catheter within the heart with an external magnetic field rather than manual catheter control. METHODS: Thirty-one adults referred for diagnostic electrophysiology studies were enrolled in a prospective trial of the MGS. The magnetic catheter was navigated to preselected sites in the right atrium (RA) and right ventricle (RV) in the first 20 patients. Electrograms were recorded at each target site, and pacing thresholds were measured. In a subset of five patients, RA and RV electrograms and stimulation thresholds were recorded with both a standard ablation catheter and the magnetic catheter. Eleven additional patients were recruited for supraventricular tachycardia (SVT) mapping, and seven of these underwent ablation. RESULTS: Navigation was successful in 200 of 202 predetermined right-sided navigation targets and 13 of 13 targets in the left atria. Pacing thresholds and electrogram amplitudes in the RA and RV were not significantly different between the standard and magnetic catheters. The SVT mapping with the magnetic catheter was successful in 13 patients, including 4 with left-sided accessory pathways. The MGS was used for successful ablation of SVT in seven of seven patients. There were no procedural complications. CONCLUSIONS: These results demonstrate that the MGS can be used for intracardiac mapping, pacing, and ablation safely and effectively.     

Trauma-induced proliferation of astrocytes in the brains of young and aged rats

The time-course and magnitude of astrocyte proliferation following neural trauma was evaluated in young adult (3 months) and mid-aged (16-19 months) male Fischer 344 rats. One to 4 days after a needle wound was made through the cortex and the hippocampus, rats received three intraperitoneal injections of 3H-thymidine at 8 hour intervals and were sacrificed 1 hour after the last injection. For astrocyte quantification, 3H-thymidine autoradiography was combined with immunohistochemical staining for glial fibrillary acidic protein followed by semithin sectioning. In areas of the cortex and hippocampus adjacent to the wound, astrocytes were categorized as unlabeled or labeled with silver grains over the nuclei. Labeling index and numerical density of astrocytes were determined using stereological methods. The results showed that in both young and older rats, astrocyte proliferation is an early glial response to neural trauma, occurring during the first 4 postlesion days and contributing to an increase in astrocyte population. Regional differences in labeling index and numerical density suggest heterogeneity in the proliferative capacity of astrocyte subpopulations in the rat brain. Compared with young animals, older rats demonstrated greater labeling in the cortex but not in the hippocampus. Thus, aging is associated with region-specific increase in astrocyte reactivity to trauma possibly due to increased availability of mitogens or enhanced sensitivity of astrocytes to mitogenic signals.     

Cardiac resynchronization therapy acutely improves diastolic function.

BACKGROUND: Invasive studies have shown that cardiac resynchronization therapy (CRT) acutely improves left ventricular (LV) systolic performance and lowers filling pressures in a majority of patients with medically-refractory severe heart failure. Measurements included LV volume, ejection fraction, PWD early (E-wave) and atrial (A-wave) velocities, diastolic filling time (DFT), and DTI early diastolic mitral annular velocity (Em) at the lateral and septal annulus; PWD mitral E-wave/Em and E/FP were calculated to estimate LV filling pressures. RESULTS: Immediately after CRT, LV volumes decreased and LVEF increased significantly. PWD mitral E-wave velocity decreased and E-wave duration and DFT increased significantly; mitral E/FP ratio also decreased significantly, consistent with a decrease in LV filling pressure. Patients with a pre-CRT mitral E/A ratio >1 (n = 20), demonstrated improvements in LV diastolic filling and lower filling pressures whereas those with an E/A ratio < or =1 (n = 21) did not show significant changes in diastolic indices. CONCLUSIONS: The acute effects of CRT include echocardiographic evidence of reduced LV volumes and increased LVEF with improved diastolic filling and lower filling pressures; LV relaxation is not significantly altered. The benefits in diastolic function are dependent on the PWD-determined LV filling characteristics prior to CRT.     

Repolarization changes underlying long-term cardiac memory due to right ventricular pacing: noninvasive mapping with electrocardiographic imaging

Background- Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results- Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. Conclusions- These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.     

Improvements in left ventricular diastolic function after cardiac resynchronization therapy are coupled to response in systolic performance.

OBJECTIVES: To determine the short-term effects of cardiac resynchronization therapy (CRT) on measurements of left ventricular (LV) diastolic function in patients with severe heart failure. BACKGROUND: Cardiac resynchronization therapy improves systolic performance; however, the effects on diastolic function by load-dependent pulsed-wave Doppler transmitral indices has been variable. METHODS: Fifty patients with severe heart failure were evaluated by two-dimensional Doppler echocardiography immediately prior to and 4 +/- 1 month after CRT. Measurements included LV volumes and ejection fraction (EF), pulsed-wave Doppler (PWD)-derived transmitral filling indices (E- and A-wave velocities, E/A ratio, deceleration time [DT], diastolic filling time [DFT], and isovolumic relaxation time). Tissue Doppler imaging was used for measurements of systolic and diastolic (Em) velocities at four mitral annular sites; mitral E-wave/Em ratio was calculated to estimate LV filling pressure. Color M-mode flow propagation velocities were also obtained. RESULTS: After CRT, LV volumes decreased significantly (p < 0.001) and LVEF increased >5% in 28 of 50 patients (56%) and were accompanied by reduction in PWD mitral E-wave velocity and E/A ratio (both p < 0.01), increased DT and DFT (both p < 0.01), and lower filling pressures (i.e., E-wave/Em septal; p < 0.01). Patients with LVEF response < or =5% after CRT had no significant changes in measurements of diastolic function; LV relaxation (i.e., Em velocities) worsened in this group. CONCLUSIONS: In heart failure patients receiving CRT, improvement in LV diastolic function is coupled to the improvement in LV systolic function.     

Remote controlled magnetically guided pulmonary vein isolation in canines

BACKGROUND: Ablation of atrial fibrillation (AF) remains a challenging procedure fraught with significant risks and technical difficulties. A magnetically guided catheter system has been developed that potentially addresses many of these challenges. Fully remote controlled electrical isolation of pulmonary veins was performed in canines, facilitated by a three-dimensional computed tomogram (CT) that depicted the anatomic relationships of the pulmonary veins and the left atrium. OBJECTIVE: The purpose of this study was to evaluate the feasibility of pulmonary vein isolation with a novel remote controlled magnetically guided catheter. METHODS: CT scans were obtained in seven healthy male canines. A 7-Fr irrigated magnetic catheter was advanced transseptally to the left atrium. A magnetic guidance system was used to control the orientation of the catheter tip. A mechanical device advanced or retracted the catheter as needed. Pulmonary venography was performed and compared with the CT scan. The CT scan was used as a visual reference to set the magnetic field vectors. Radiofrequency energy was delivered through the irrigated magnetic catheter to isolate the superior pulmonary veins, as judged by elimination of pulmonary vein potentials. RESULTS: The isolation procedure was successful in all 14 pulmonary veins, and there was no evidence of stenosis at 80-100 days postprocedure. CONCLUSIONS: These results demonstrate that remote controlled catheter ablation is safe and effective for segmental pulmonary vein isolation. This technology could facilitate curative ablation of AF in humans and reduce the occupational hazards to the operator of prolonged procedures and radiation exposure.