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Atrial septal defects (ASDs) and patent foramen ovale (PFOs) are both interatrial septal defects, which are among the most common congenital heart diseases in children and adults. When indicated for closure, the first choice of treatment is percutaneous (transcatheter) closure. This thesis aims to investigate the impact of percutaneous closure on symptoms, ventilation, hemodynamics, electrophysiology, and mechanics in adult ASD patients, and that of symptoms and secondary prevention of stroke in PFO patients.

Chronic total coronary occlusions (CTO) remain the most complex lesions for percutaneous revascularization. Historically, percutaneous coronary intervention of CTO was hampered by high rates of restenosis and reocclusions. The introduction of drug-eluting stents significantly improved the treatment of CTO-PCI by reducing the rate of restenosis and reocclusions. In this thesis we investigated bare metal stents and first, second -and third-generation drug-eluting stents (DES) in CTO. In the first part we focus on the efficacy and clinical safety of these stents in three multi-centre randomized clinical trials. In Chapter 2 , we showed that intima proliferation is continuous at the long-term with first generation and not halted by DES. In Chapter 3 and 4 we showed worse angiographic outcome with second-generation Endeavor zotarolimus-eluting stents compared to first-generation Sirolimus-eluting stents (SES). On the other hand, non-inferiority could be established with second-generation Resolute zotarolimus-eluting stent compared to SES. In Chapter 4-8 we compared the second-generation thin-strut everolimus-eluting stent (EES) to the third-generation ultra thin-strut sirolimus-eluting stent (Hybrid SES). At 9-month, primary non-inferiority angiographic endpoint was not met for Hybrid SES with higher rate of binary restenosis compared to EES. The difference in outcome was mostly attributed in the sub-group of smaller stent diameters. EES showed higher rates of uncovered stent struts, on the other hand Hybrid SES demonstrated higher rates of malapposition and evaginations. In the last part Chapter 9 and 10 , we showed that residual distal stenosis behind the CTO could be safely deferred from immediate stenting and that continuous thermodilution is a promising technique to investigate the coronary physiology.

The burden of heart failure (HF) remains high, with worrisome morbidity and mortality rates for patients hospitalized for acute decompensated heart failure (ADHF). The natriuretic peptides, BNP and the inactive N-terminal fragment of its precursor proBNP (NT-proBNP), which are released in response to cardiac wall stretch, are used for both diagnostic and prognostic purposes. Prognostication is especially important, because it allows clinicians to triage patients during and after hospitalization. This thesis aimed to unravel the role of NT-proBNP in the risk stratification and management of these high-risk patients. First, we build a simple, yet robust bedside discharge score, the ELAN-HF score (European coLlaboration on Acute decompeNsated Heart Failure), incorporating NT-proBNP levels at discharge as well as the dynamic change during hospitalization, predicting 6-months all-cause mortality. Additionally, other important risk factors of prognosis in ADHF were compared with NT-proBNP levels. Moreover, we studied a relatively unknown area of NT-proBNP use for prognosis and possibly management, as it concerns patients with preserved ejection fraction (HFpEF). Finally, the use of NT-proBNP as a guiding tool for patients hospitalized for ADHF was tested by conducting an international randomized study on in-hospital guidance of HF therapy by predefined NT-proBNP target. The aim was to decrease mortality and HF readmission rates 6 months after discharge, however the study showed that NT-proBNP-guided therapy did not improve outcome. Therefore, we conclude that natriuretic peptides in patients hospitalized for ADHF are to be used as a risk stratification tool at discharge without any consequence for follow-up or guiding strategies.

A chronic total occlusion (CTO) is the most extreme form of coronary artery disease (CAD). Patients with a CTO have a worse clinical outcome compared to non-CTO patients, irrespective of age or other co-morbidities. Especially patients presenting with a ST-segment elevation myocardial infarction (STEMI), in whom (accidently) a concurrent CTO is found, have increased morbidity and mortality. In contrary invasive treatment of CTO lesions is infrequently performed. The question whether routine early percutaneous coronary intervention (PCI) of the concurrent CTO after successful primary PCI for STEMI will lead to improved outcome is the main endpoint of the Evaluating Xience and LV Function in PCI on Occlusions After STEMI (EXPLORE) trial. The thesis presented here is an in-depth exploration of this important question.

In patients presenting with a ST-segment elevated myocardial infarction (STEMI) reperfusion therapy should be initiated without delay. Patients are immediately transported to the catheterization laboratory to start primary percutaneous coronary intervention (PCI). Primary PCI is directed at removal of the occlusive thrombus and restoration of epicardial flow using implantation of a coronary stent. Nowadays, more than ninety-five percent of the admitted STEMI patients, not presenting with shock, survive the initial phase of myocardial infarction. This thesis addresses the possible complications that survivors of STEMI are faced with, ranging from radiation exposure, bleeding and thrombo-embolic events to ventricular arrhythmias and adverse left ventricular (LV) remodeling. In the last part of the thesis studies are presented that investigate the effects of intracoronary BMMC therapy as an adjunctive therapy to improve STEMI outcomes.

The combined pressure-conductance catheter provides the opportunity to continuously assess systolic and diastolic LV function from pressure-volume loops in the catheterization laboratory, enabling accurate assessment of the timing and magnitude of the LV dynamic effects of therapeutic interventions. The purpose of this thesis is to investigate LV and coronary hemodynamic effects in the setting of PCI. In general, the thesis consists of four parts. The first part describes the effects of repeated episodes of acute myocardial ischemia on LV dynamic characteristics. The second part describes LV function and hemodynamic effects during primary PCI in STEMI patients. The third part concerns the evaluation of the safety, feasibility, and efficacy of a new LV unloading device for support in high-risk and primary PCI patients. The fourth part focuses on LV function recovery and its influence on the coronary microcirculation after primary PCI. This includes a discussion on the role of mechanical support in the setting of revascularization in acute myocardial infarction.