br Conflict of interest br Introduction Cardiac resynchroniz
Conflict of interest
Introduction Cardiac resynchronization therapy (CRT) has become an important treatment for the management of AZD0530 cost failure (HF) patients with left ventricular (LV) systolic dysfunction and a ventricular conduction delay [1,2]. Multiple randomized studies have demonstrated improvements in symptoms and cardiac function as well as reductions in morbidity and mortality in appropriately selected patients with moderate to severe HF despite optimal medical therapy [3–7]. More recent studies have also demonstrated benefit in patients with milder forms of HF, which has expanded the population eligible for device-based therapy [8–10]. A response to CRT is not guaranteed, as approximately 30% of patients do not appear to experience significant clinical improvement . This proportion of non-responders varies with the measure used, but clearly there is an opportunity to improve the effectiveness of this therapy. Given the inherent risks and costs of device implantation and maintenance, a reduction in the rate of CRT “non-responders” is an important goal. Improvements in patient selection and device optimization are two available strategies that can potentially increase the proportion of patients who respond to CRT. With regard to the former, measures of mechanical dyssynchrony to select patients have been disappointing. Indeed, the multicenter PROSPECT trial failed to identify any single echocardiographic marker of dyssynchrony that was predictive of response to CRT . There are other promising techniques such as pacing at sites of late mechanical or electrical activation, and avoiding pacing in patients with significant left ventricular scar. Device optimization post-implantation includes individualized programming of the atrioventricular (AV) and ventriculo-ventricular (VV) delay to maximize the hemodynamic and, hopefully, clinical response to CRT. While early CRT devices allowed AV delay programming with simultaneous biventricular (BiV) pacing, modern systems allow programming of both the individual AV and VV intervals. Considering additional variables such as the AV delay offset for atrial-sensed (AS) vs. atrial-paced (AP) CRT and rate-adaptive AV delay modulation, the complexity of CRT programming is obvious. There are multiple strategies for AV and VV optimization without a clear “gold standard” for comparison, which makes interpretation of available data challenging. Guidelines for CRT also do not provide recommendations for optimization of these parameters, reflecting a lack of consensus on this issue [1,2]. Despite these limitations, AV and VV optimization may prove useful in select patients with CRT, and a working understanding of the methods and controversies involved is important for all physicians who manage these patients.
AV optimization The importance of AV synchrony is intuitive, as preservation of both passive and active LV filling contribute to stroke volume and cardiac output. Interestingly, AV optimization may be more useful to resynchronize the left ventricle electrically than to optimize filling. Early studies in patients with complete heart block and dual chamber pacemakers confirmed variation in stroke volume with changes in programmed AV delay . In CRT, in which the majority of patients have preserved intrinsic AV nodal conduction but prolonged inter- and intraventricular conduction, AV delay programming has also been correlated with changes in LV systolic function, as measured invasively by dP/dt. As a result, methods of AV delay optimization have been the focus of numerous studies using approaches that focus on optimization of either LV diastolic or systolic function, primarily through use of Doppler echocardiography (Fig. 1). Furthermore, all of the major trials of CRT in HF patients, with the exception of the CONTAK-CD trial , performed some method of AV delay optimization.