Cardiac resynchronization devices: the Food and Drug Administration's regulatory considerations.

Cardiac resynchronization therapy (CRT) devices have been studied clinically since 1998, and have been on the U.S. market since the Food and Drug Administration (FDA) approval of the first product in 2001.

Evidence of structural remodeling in the dyssynchronous failing heart.

Ventricular remodeling of both geometry and fiber structure is a prominent feature of several cardiac pathologies. Advances in MRI and analytical methods now make it possible to measure changes of cardiac geometry, fiber, and sheet orientation at high spatial resolution. In this report, we use diffusion tensor imaging to measure the geometry, fiber, and sheet architecture of eight normal and five dyssynchronous failing canine hearts, which were explanted and fixed in an unloaded state.

A US Food and Drug Administration perspective on cardiac resynchronization and ventricular assist device trials.

Cardiac resynchronization therapy and ventricular assist devices are two of the many US Food and Drug Administration-regulated medical device technologies that are intended for patients with heart failure. Cardiac resynchronization therapy devices have been shown to significantly improve the quality and potentially the duration of life for patients with moderate-to-severe congestive heart failure and electrical dyssynchrony. Likewise, ventricular assist devices have benefited patients with end-stage heart failure through both bridge-to-transplant and destination therapy.

Cardiac dyssynchrony analysis using circumferential versus longitudinal strain: implications for assessing cardiac resynchronization.

Background: QRS duration is commonly used to select heart failure patients for cardiac resynchronization therapy (CRT). However, not all patients respond to CRT, and recent data suggest that direct assessments of mechanical dyssynchrony may better predict chronic response. Echo-Doppler methods are being used increasingly, but these principally rely on longitudinal motion (epsilonll).

Timing of depolarization and contraction in the paced canine left ventricle: model and experiment.

Introduction: For efficient pump function, contraction of the heart should be as synchronous as possible. Ventricular pacing induces asynchrony of depolarization and contraction. The degree of asynchrony depends on the position of the pacing electrode.

Torsion of the left ventricle during pacing with MRI tagging.

The effects of different pacing protocols on left ventricular (LV) torsion were evaluated over the full cardiac cycle. A systolic and diastolic series of magnetic resonance imaging (MRI) scans were combined and used to calculate the torsion of the LV in a canine model. The asynchronous activation resulting from ventricular pacing interferes with the temporal evolution of LV torsion.

Regional alterations in protein expression in the dyssynchronous failing heart.

Background: Left ventricular (LV) mechanical dyssynchrony induces regional heterogeneity of mechanical load and is an independent predictor of mortality and sudden death in heart failure (HF) patients. We tested whether dyssynchrony also induces localized disparities in the expression of proteins involved with mechanical stress, function, and arrhythmia susceptibility.

Methods And Results: Eleven dogs underwent tachycardia-induced HF pacing, either from the right atrium or high right ventricular free wall.

Endocardial versus epicardial electrical synchrony during LV free-wall pacing.

Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony (fusion with intrinsic conduction) is important.

Novel technique for cardiac electromechanical mapping with magnetic resonance imaging tagging and an epicardial electrode sock.

Near-simultaneous measurements of electrical and mechanical activation over the entire ventricular surface are now possible using magnetic resonance imaging tagging and a multielectrode epicardial sock. This new electromechanical mapping technique is demonstrated in the ventricularly paced canine heart. A 128-electrode epicardial sock and pacing electrodes were placed on the hearts of four anesthetized dogs.

Electromechanical mapping with MRI tagging and epicardial sock electrodes.

Methods currently exist for the precise measurement of local three-dimensional myocardial motion noninvasivly with magnetic resonace imaging tagging. From these motion estimates, strain images representing the local deformation of the myocardium can be formed to show local myocardial contraction. These images clearly show the sequence of mechanical events during the activation and relaxation of the heart, making them ideal to visualize abnormalities caused by asynchronous electrical activation or ischemia.

Systolic improvement and mechanical resynchronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block.

Background: Biventricular (BiV) and left ventricular (LV) pacing similarly augment systolic function in left bundle-branch block (LBBB)-failing hearts despite different electrical activation. We tested whether electrical synchrony is required to achieve mechanical synchronization and functional benefit from pacing.

Methods And Results: Epicardial mapping, tagged MRI, and hemodynamics were obtained in dogs with LBBB-failing hearts during right atrial, LV, and BiV stimulation.

Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction.

Resynchronization is frequently used for the treatment of heart failure, but the mechanism for improvement is not entirely clear. In the present study, the temporal synchrony and spatiotemporal distribution of left ventricular (LV) contraction was investigated in eight dogs during right atrial (RA), right ventricular apex (RVa), and biventricular (BiV) pacing using tagged magnetic resonance imaging. Mechanical activation (MA; the onset of circumferential shortening) was calculated from the images throughout the left ventricle for each pacing protocol.