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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.

This thesis focuses on a novel stent technology: the nitinol self-apposing STENTYS stent. This nitinol stent has the ability to appose itself to variable vessel diameters which might overcome some limitations of stiff tubular balloon-expanded stents. First, we evaluated the properties and clinical performance of the STENTYS stent. Then the novel delivery device and possible difficulties or complications using this device was investigated. With the use of intracoronary imaging techniques, it was possible to assess detailed analyses of the arterial wall and the stent strut apposition, as well as stent related complications.

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.

During the last decade, there has been a rapid increase in the use of MitraClip implantation and TAVI worldwide. Both percutaneous techniques are valuable therapies when the conventional surgery is not an option due to high surgical risk. Both techniques have been shown to be effective and safe treatment options in this high-risk patient population. For this reason, these techniques have been included in the current valvular guidelines. Several studies have reported acceptable mid-term survival rates while complication rates are low. More studies were needed in order to further improve the safety and efficacy by obtaining a better insight in which patients would benefit most from these therapies. Furthermore we wanted to improve selection criteria and study the effect of these techniques on left- and right ventricular function and inflow patterns and related these to the symptomatic status of the patients.

Tegenwoordig gebruiken ziekenhuizen een nieuwe stent bij dotterbehandelingen van kransslagadervernauwingen. Deze Genous-stent heeft een laag met antistoffen waardoor het behandelde bloedvat snel bedekt raakt met lichaamseigen cellen. Zo wordt tegengegaan dat er opnieuw een vernauwing optreedt of dat er zich stolsels gaan vormen. Voordeel is dat patiënten maar kort antistollingsmedicijnen nodig hebben. Uit het onderzoek van Margo Klomp blijkt dat patiënten met diabetes, ouderen en patiënten met gevorkte vernauwingen goed behandeld kunnen worden met de stent. Bij patiënten met complex vaatlijden lijkt de stent over een periode van twaalf maanden minder effectief dan medicijnafgevende stents, maar er is langere follow-up nodig voor een goede vergelijking.

Inzet van een AED bij mensen met een plotse hartstilstand buiten het ziekenhuis verdubbelt de overlevingskans. Dat heeft onderzoeker Jocelyn Berdowski van het Academisch Medisch Centrum (AMC) in Amsterdam vastgesteld in een onderzoek naar de hele keten van hulpverlening bij een plotselinge hartstilstand buiten het ziekenhuis. Als de AED ter plaatse hangt kan de overlevingskans zelfs verdrievoudigen maar het wordt nog te weinig toegepast. De overleving is volgens Berdowski na een plotse hartstilstand in de afgelopen tien jaar bijna verdubbeld van 9 naar 17 procent. Berdowski noemt het ook zeer belangrijk dat een meldkamercentralist de hartstilstand herkent. Dat bleek in 70 procent van alle meldingen van hartstilstand het geval. Als de centralist meteen weet waar het om gaat is de kans op overleven 14 procent, maar als dat niet duidelijk is, daalt de overlevingskans naar slechts 5 procent. De helft van de patiënten met een schokbare hartritmestoornis overleeft het als ze de schok binnen 6 minuten krijgen. De reanimatierichtlijn van 2005 voor mensen met een plotse hartstilstand buiten het ziekenhuis heeft naast verbeteringen, ook problemen aan het licht gebracht ten opzichte van de richtlijn uit 2000. Om de vijf jaar worden de richtlijnen voor reanimatie vernieuwd. Nieuw in de richtlijn van 2005 was dat bij hartstilstand direct na toediening van de schok meteen gestart moest worden met hartmassage. Veel hartmassage is positief, maar daardoor blijven mensen ook wat langer in een schokbaar hartritme en dat is niet goed. Berdowski pleit voor onderzoek naar een techniek waarbij het schokbare ritme van het hart te bekijken is zonder dat de hartmassage beëindigd moet worden.

Ondanks het feit dat het electrocardiogram meer dan een eeuw geleden werd geïntroduceerd, blijft dit instrument een essentieel onderdeel in de diagnostiek en behandeling van patiënten met acute pijn op de borst. Niels Verouden beschrijft de waarde van het 12-kanaals-electrocardiogram in zowel de diagnostiek als in de prognose van patiënten met een ST-segmentelevatie myocardinfarct die een acute dotterbehandeling ondergaan. Hij vond onder meer een nieuw patroon zonder ST-segmentelevatie dat aanwezig is bij twee procent van de patiënten met een transmuraalvoorwandinfarct. Verder blijkt uit een analyse van ruim tweeduizend patiënten dat het mogelijk is om met behulp van het electrocardiogram op de catheterisatiekamer patiënten te identificeren met een hoog risico op vroegtijdig overlijden. Deze patiënten zouden kunnen profiteren van aggressievere (medicamenteuze) therapie.

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.