Rick Schreurs

27 Exploring CRT of cardiac systole [24]. In addition, the acute improvement in LV dP/dt max may not be able to predict the clinical outcome on the long-term [25]. Long-term effects of CRT The favourable outcomes of CRT can be explained by reverse remodelling of the heart due to resynchronization of the ventricles. Remodelling can be activated through neurohormonal activation, differences in mechanical load and wall stress. Several studies in animal models of LBBB, sometimes in combination with tachypacing induced heart failure, have shed led light on the cellular and molecular adaptations in asynchronous hearts. The expression of some genes and proteins is depressed uniformly, while others show regional differences in expression between early- and late-activated areas. Changes occur related to myocyte function, calcium handling, β-adrenergic responsiveness, mitochondrial ATP synthase activity, cell survival signalling and other functions. CRT reverses many of these alterations, which will be reviewed in detail elsewhere in this journal. LV pressure (mmHg) p140 p120 p100 p80 p100 P120 p140 p80 Baseline p80 100 200 LV volume (mL) 100 200 LV volume (mL) 100 50 0 LBBB 0 months CRT 6 months Figure 3. Pressure-volume loops at baseline and after 6 months of CRT in a patient, measured at heart rates of 80, 100, 120 and 140 beats per minute. Reproduced with permission from the American Heart Association [26]. These extensive reverse-remodelling processes may also explain the improvements in pressure-volume diagrams recorded after 6 months of CRT ( Figure 3 ). Note that after 6 months end diastolic volume and end systolic volume show a leftward shift, while ejection fraction increases [26]. Moreover, while before CRT the loops decrease in size with increased heart rate, this was much less the case after 6 months of CRT, indicating better pump function. Other studies report higher ejection fraction and lower end-systolic ventricular dimensions after one year of follow-up [24, 27]. A study in the LBBB canine model shows that acute CRT restores dP/dt max almost back to pre-LBBB values and chronic CRT increases it slightly further, yet not completely back to pre-LBBB values [12]. 2