The promise of resynchronization therapy. Who (and how many) will benefit?

It has been estimated that about 320,000 to 400,000 patients in the USA alone are possible candidates to cardiac resynchronization therapy according to the recently published AHA/ACC/NASPE guidelines for pacing and the results of the COMPANION trial. The selection of the most suitable candidate for CRT/CRTD is a crucial issue, but still a matter of debate. A large variety of clinical, invasive and non-invasive criteria have been proposed for appropriately selecting candidates for CRT. However, in all the studies the parameters have been retrospectively identified and none has reported their results in the form of a multivariate regression model. We have now well characterized the patients in sinus rhythm who most likely benefit from this non-pharmacological approach. The fact that the COMPANION trial was able to single out a specific subgroup of heart failure patients that can be treated better than what was very short time ago best medical therapy validates the large body of research that investigators worldwide have created about this therapy. Finally, the concept that any patients that require ventricular pacing, who have heart failure class II/III or IV may benefit from receiving biventricular rather than right ventricular pacing as much as the other patients with more classical indication for CRT is still open to discussion and needs to be tested in a randomized multicenter trial.

Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay.

We characterized the relationship between systolic ventricular function and left ventricular (LV) end-diastolic pressure (LVEDP) in patients with heart failure (HF) and baseline asynchrony during ventricular stimulation. The role of preload in the systolic performance improvement that can be obtained in HF patients with LV stimulation is uncertain.We measured the maximum rate of increase of LV pressure, LVEDP, aortic pulse pressure (PP) and the atrioventricular mechanical latency (AVL) between left atrial systole and LV pressure onset in 39 patients with HF. Two subgroups were identified: "responder" if PP improved, or "nonresponder."Maximum hemodynamic improvement occurred at an atrioventricular (AV) delay that did not decrease LVEDP. Left ventricular and biventricular (BV) stimulation increased systolic hemodynamics significantly, despite no significant increase in LVEDP. All parameters decreased when the LVEDP was decreased by shorter AV delay. Left ventricular and BV stimulation provided better hemodynamics than right ventricular (RV) stimulation. For the nonresponder subgroup, systolic hemodynamics only worsened during AV delay shortening. For the responder subgroup, optimum PP was achieved when AVL was near zero. Restoration of optimal left atrial-ventricular mechanical timing partly contributes to the hemodynamic improvements observed in this patient subgroup. However, preload alone cannot explain the differences seen between RV and BV stimulation and the contradictory PP decreases even at maximal preload in the nonresponder subgroup. These results may be explained by a site-dependent mechanism such as the degree of ventricular synchrony. Caution should be taken in these patients when optimizing AV delays using echocardiography techniques that focus on LV inflow.

Effect of cardiac resynchronization therapy on ventricular remodeling.

Cardiac resynchronization therapy (CRT) is a new non-pharmacological option for patients with advanced heart failure and ventricular conduction delay. Four randomized prospective studies have provided evidence that CRT increases exercise capacity, improves functional class and quality of life. There is also increasing evidence that CRT may trigger an inverse remodeling process leading to reduction of ventricular diameter and eventually of the atrial size. The pathophysiological mechanism throughout CRT may promote inverse remodeling is: (1) reduction of systolic and diastolic mitral regurgitation; (2) reduction of sympathetic/parasympathetic imbalance as well as reduction of neurohumoral activation due to increased systolic blood pressure and improved filling time; (3) reduction of regional wall stress. The structural changes taking place during CRT are directly related to continuous pacing, because lack of pacing immediately shows the new onset of remodeling. The duration of the reported changes of ventricular diameter is still unknown, and it is also unknown whether such reverse remodeling process of the ventricle and of the atria will lead to a reduction of cardiac death and incidence of ventricular arrhythmias.