What is treatment success in cardiac resynchronization therapy?

Abstract

Cardiac resynchronization therapy (CRT) is an established treatment for symptomatic patients with heart failure, a prolonged QRS duration, and impaired left ventricular (LV) function. Identification of 'responders' and 'non-responders' to CRT has attracted considerable attention. The response to CRT can be measured in terms of symptomatic response or clinical outcome, or both. Alternatively, the response to CRT can be measured in terms of changes in surrogate measures of outcome, such as LV volumes, LV ejection fraction, invasive measures of cardiac performance, peak oxygen uptake, and neurohormones. This review explores whether these measures can be used in assessing the symptomatic and prognostic response to CRT. The role of these parameters to the management of individual patients is also discussed.

Figure 1

Relationship between disease processes, interventions, surrogate endpoints, and true clinical outcome. (A) The ideal situation, which offers the greatest potential for the surrogate to be valid; (B) the surrogate is not in the aetiological pathway of the disease; (C) the intervention affects only the pathway mediated through the surrogate, but there are other aetiological pathways; (D) the intervention does not affect the surrogate; (E) the mechanism of action of the intervention is independent of the disease process. Dotted lines represent other possible mechanisms of action. Adapted with permission from Fleming TR and DeMets DL.

Figure 2

Reciever-operating curves for predicting all-cause (A) and cardiovascular (B) mortality by LV reverse remodelling, as reflected by the reduction in LVESV (dark line) and LVEDV (light line). Reproduced with permission from Yu CM, et al.

Figure 3

Acute haemodynamic changes in patients with CRT-on and CRT-off. Changes pertain to patients with advanced decompensated heart failure who had undergone CRT implantation at least 3 months prior to testing. A significant worsening of haemodynammics was observed immediately after CRT was programmed off. Reproduced with permission from Mullens et al.

Figure 4

Effect on ejection fraction of carvedilol and placebo in the Australia-New Zealand (ANZ) carvedilol study, enalapril and placebo in the SOLVD study.

Figure 5

Receiver-operating curves for peak VO₂ in relation to 3 year survival. The area under the curve was significantly greater for peak VO₂ than for age and ejection fraction (P < 0.05). Reproduced with permission from Myers et al., EF, left ventricular ejection fraction.