Understanding Mechanisms of Cardiac Resynchronization Therapy Response to Improve Patient Selection and Outcomes

edical therapy for systolic heart failure improves symptoms, functional capacity, and survival.However, despite optimal medical therapy, many patients with significantly depressed left ventricular (LV) systolic function continue to have symptoms that limit functionality and quality of life.Deleterious hemodynamics effects of asynchronous activation of the myocardium have been recognized for almost a century. 1 Many patients with LV dysfunction have additional interventricular or intraventricular dyssynchrony, which can further impair cardiac output 2 and which, in some cases, may be the primary cause of LV dysfunction itself. 3Ventricular dyssynchrony results in adverse changes in ventricular loading and hemodynamics, cardiac blood flow and energy metabolism, gene and protein expression, and valvular regurgitation, eventually culminating in progressive adverse ventricular remodeling, which can cause further deterioration of LV function. 4Cardiac resynchronization therapy (CRT) targets and treats ventricular dyssynchrony and has been associated with reduced heart failure hospitalization, improved functional status, better quality of life, and decreased mortality in multiple randomized controlled trials (RCTs). 5RT implantation is an invasive procedure associated with both procedural risk 6 and cost.Unfortunately, all patients who meet current guidelines for CRT implantation 7 (which focus primarily on LV ejection fraction, New York Heart Association functional class, and QRS duration/morphology) do not experience benefit from CRT, and despite extensive study, optimal patient selection for CRT remains elusive.QRS duration, left bundle branch block (LBBB), and other clinical and demographic parameters have been associated with rates of CRT response, 8 and CRT implantation using echocardiographic 9 or electrogram-guided 10 LV lead positioning have been proposed as ways to improve CRT response rates, but even with improved technology, ≈30% of patients remain CRT nonresponders and do not experience significant benefit from the procedure. 11Novel methods of improving patient selection for CRT are needed.In this issue of Circulation: Arrhythmia and Electrophysiology, Huntjens et al 12 present results from a study in which computational modeling (using the Circ-Adapt model) of variations in interventricular (right ventricle [RV] to LV) and intraventricular (within the LV) dyssynchrony were used to predict the acute effects of CRT as manifest by increases in LV maximum dP/dt (LV dP/dt max ).Computer modeling demonstrated that increasing degrees of interventricular dyssynchrony (defined as the difference between mean RV free wall activation time and mean LV free wall activation time) resulted in the largest improvements in dP/dt max and therefore would be expected to result in improved rates of clinical CRT response.However, intraventricular dyssynchrony (defined as LV total activation time or the EDITORIAL