Rick Schreurs

145 Impact IMPACT In 2019 nearly 250.000 people suffered from heart failure in the Netherlands, leading to almost 30.000 cases of hospitalization [1]. All-cause-mortality in patients with heart failure is 7% and even increases to 17% in case of hospitalization [2]. The total health care costs of heart failure in the Netherlands were 817 million euros in 2017 [1]. Besides trying to take away the underlying cause of heart failure, treatment consists of lifestyle changes and pharmacotherapy to reduce cardiac stress and filling pressures. Approximately a quarter of all patients with heart failure also have electrical conduction disorders, mainly left bundle branch block (LBBB). These patients may benefit from cardiac resynchronization therapy (CRT) as adjunct therapy [3]. CRT synchronizes the electrical activation and thereby contraction of the left and right ventricle (RV) using biventricular (BiV) pacing and thereby improve the overall cardiac output. In the Netherlands about 12.500 pacemakers were implanted in 2019 of which 2.500 were CRT devices [4]. Although CRT provides great reductions in heart failure burden on the population level, individual response varies significantly. The main objectives of this thesis were: 1) to study whether BiV pacing could also improve cardiac function in patients with first-degree AV-block and 2) to examine how the optimal benefit of CRT could be achieved by optimizing the delay between atrial and ventricular activation (AV-delay). In this chapter we summarize the clinical and societal impact of the main findings of this thesis. Clinical impact In chapter 3 we showed that restoring physiological AV-delays using BiV pacing increased cardiac pump function in heart failure patients with first-degree AV-block who did not have clear intraventricular conduction disorders. Therefore, this acute hemodynamic study suggests that indications for CRT may be extended to patients who have heart failure and a first-degree AV-block. Obviously, larger and long-term studies are required to support this idea before it can be added to the CRT-guidelines. Additionally, the results in chapter 3 implicated that the benefits that were achieved by restoring AV-coupling were reduced by cardiac dyssynchrony as induced by RV pacing, indicating that restoration of AV coupling by pacing therapy should be performed while maintaining as much as possible the normal ventricular conduction. In chapter 3 we also showed that optimizing the AV-delay in a porcine healthy heart resulted in greater cardiac output. This implicates that patients with first-degree AV-block but without heart failure might benefit from cardiac pacing as well. We hypothesize that pacing therapy in these patients does not necessarily treat symptoms, but may prevent the development of heart failure, and thereby decreases morbidity and mortality. Again, before this therapy can be broadly introduced in the clinic, additional research and preferably randomized controlled trials need to be done. These studies should not only focus on which patients are most eligible for the therapy but also which pacing modality shows the optimal result. As mentioned before maintaining ventricular synchrony is a must, something which I