title: Rethinking Resynch: Exploring Mechanisms of Cardiac Resynchroniztion Beyond Wall Motion Control.
abstract: Cardiac resynchronization (CRT) is a widely used clinical treatment for heart failure patients with depressed function and discoordinate contraction due to conduction delay. It is unique among heart failure treatments as it both acutely and chronically enhances systolic function yet also prolongs survival. While improved chamber mechano-energetics has been considered a primary mechanism for CRT benefit, new animal model data are revealing novel and in many instances unique cellular and molecular modifications from the treatment. Examples of these changes are the reversal of marked regional heterogeneity of the transcriptome and stress kinase signaling, improved ion channel function involved with electrical repolarization, enhanced sarcomere function and calcium handling and upregulation of beta-adrenergic responses, and improved mitochondrial energetic efficiency associated with targeted changes in the mitochondrial proteome. Exploration of these mechanisms may reveal key insights into how CRT can indeed get the failing heart to contract more and perform more work, yet not worsen long-term failure. These changes may provide a more biological marker for both the appropriate patients for CRT as well as point the way for new therapeutic avenues for heart failure in general.
authors.affiliation: Division of Cardiology Department of Medicine The Johns Hopkins University Medical Institutions Baltimore, Maryland.
authors.forename: Khalid
authors.initials: K
authors.lastname: Chakir
authors.forename: David A
authors.initials: DA
authors.lastname: Kass