1,721,061 research outputs found
Through the multidimensional looking glass: Novel perspectives on heart failure
No full textHeart failure is a deadly chronic cardiovascular disease which affects millions of people worldwide. The rapid increase of new heart failure cases globally urges a necessary shift in the current approaches. This thesis underscored the importance of broadening the perspectives of scientific research in heart failure: by adding the dimension of time (4D) – in terms of circadian rhythms and daily fluctuations – and by using advanced 3D in vitro models that adequately recapitulate native human myocardium, we gained novel insights into this deadly disease. We showed that circadian rhythms can indeed be used to improve clinical interventions, diagnosis and prognosis of heart failure patients, and offered an overview of sources suitable to study these rhythms both in human health and disease. We showed the importance of taking timing into account when measuring prognostic biomarker sST2 concentration as well as pinpointed the optimal time of day to measure pulmonary artery pressures with CardioMEMS sensors. Furthermore, we characterized circadian rhythmicity in heart failure patients and showed that the rhythmic expression of the main endocrine products of the central clock, melatonin and cortisol, is dampened when compared to the healthy controls, thus opening exciting opportunities to develop new interventions targeting the circadian clock. Lastly, we designed a mechanically tunable 3D in vitro model of human cardiac fibrosis to study its mechanistic properties, as well as for it to serve as a tissue-specific drug testing platform. Overall, with the work in this thesis, we set the stage for novel dimensions of diagnostic, prognostic and therapeutic approaches in heart failure
Idiopathic ventricular fibrillation: Absence of evidence is not evidence of absence
No full textSudden cardiac death is a major problem in the Western world. In young people, sudden cardiac arrest is often caused by ventricular fibrillation (VF). In most cases of VF, an underlying cause is found. However, in a small part of the patients, no cause for VF can be found. These patients are diagnosed with “idiopathic ventricular fibrillation” (IVF). Extensive diagnostic testing is necessary to exclude any underlying diseases. In this dissertation, we have attempted to further unravel the mystery surrounding IVF. Using a large national IVF database, we unraveled the characteristics of current IVF patients. Although adherence to (near-)complete diagnostic testing increased over the years, patients with IVF still undergo varying levels of diagnostic evaluation. This is problematic, as it leads to underdiagnosing of alternative disease. Unfortunately, as the substrate is absent in IVF, there are limited treatment options besides ICD implantation to prevent sudden cardiac death. In this thesis, we focussed on a specific phenotype in IVF, called short-coupled VF. We showed that this phenotype is prevalent in IVF. This is important, as previous research indicates that these patients can be treated effectively with class IA drugs. Another interesting region of interest in IVF patients is the mitral valve. Abnormalities in this region have been associated with ventricular arrhythmias. We were able to reveal abnormalities around the mitral valve using cardiac magnetic resonance imaging. In particular, we showed that mitral annulus disjunction is more prevalent in IVF patients compared to healthy controls. Patients with mitral valve disease proved to have a higher burden of ectopy than patients without mitral valve disease. We also applied echocardiographic deformation imaging to detect subtle myocardial abnormalities. Interestingly, both global and regional echocardiographic deformation abnormalities are more prevalent in IVF patients compared to healthy control subjects. Our research therefore indicates that subtle myocardial disease is present in a large subset of IVF patients. To search for cardiac abnormalities in family members of IVF patients, we performed familial cascade screening. We hypothesized that family members of IVF patients might reveal heritable cardiac diseases that were not apparent in the IVF patient. However, the yield of family screening in relatives of IVF patients appeared to be low when the patients was comprehensively investigated. This underlines the importance of systematic diagnostic testing in IVF. At last, we created a practical flowchart for diagnostic testing after sudden cardiac death of a young person. This is of utter importance as the current rate of diagnostic testing after sudden cardiac death in a young person is low in the Netherlands
Progress in diagnostic testing and management of idiopathic ventricular fibrillation
No full textDespite the progress in diagnostic testing and management of life-threatening arrhythmia's over the last few decades in a small part of the survivors a cause for the arrhythmia remains unknown. This group is known as idiopathic ventricular fibrillation and treatment usually consists of ICD implantation to treat any subsequent ventricular arrhythmias. The research described in this dissertation has focused on the potential of (new) diagnostic tests in this population to discover further methods for treatment and provide insight in the prognosis of both patients and their family members. The phenotypic screening of family members and diagnostic possibilities of electrocardiographic imaging are discussed
Outcomes and their determinants in patients with sudden cardiac arrest: Population health approaches to improve clinical outcomes
No full textThis thesis describes a series of academic pursuits aimed at improving SCA outcomes. It comprises an introduction, a textbook chapter, as well as ten original investigations that address current issues in improving SCA outcomes. These investigations employ a number of study designs to interrogate interrelated topics surrounding risk factors, prognostication and treatment of SCA. Specific issues explored include the use of interventional study designs other than randomized controlled trials, the use of clinical outcomes with different time horizons, recurrence of SCA, social determinants of bystander cardiopulmonary resuscitation, global prevalence and access to basic life support training, ambient air quality as a risk factor, and the evaluation of community-wide interventions aimed to improve care processes in SCA. By advancing our understanding of the risk factors, prognostication, and treatment of OHCA, we hope to improve equitable access, precision of interventions and improved clinical outcomes for our patients
Carotid Artery Stenting prior to Cardiac Surgery
No full textThis thesis describes the strategy of the management and treatment of patients with concomitant significant carotid and coronary artery disease. The short and long term outcome of a single centre experience is reported and compared with general common practise. The author conducted different observational trials in order to provide more information to justify the institutional policy. More particularly, the use of embolic protection devices in asymptomatic patients is questioned, the optimal antiplatelet therapy is investigated and the use of CT perfusion to better understand individual cerebral hemodynamics is examined.
Patients with asymptomatic carotid stenosis undergoing CAS-CABG have a decreased stroke and death rate compared to those undergoing isolated CABG or CEA-CABG. CAS may be a safer carotid revascularization option for patients with asymptomatic carotid stenosis requiring CABG in terms of postoperative stroke prevention.
In patients with symptomatic carotid stenosis available data are confounding, therefore the preferred strategy remains unclear, however carotid revascularization will result incontestably in higher periprocedural complication rates. Although level I evidence would be ideal to determine the best treatment strategy for patients who require combined treatment of carotid and coronary arterial disease, the design and implementation of a multicenter randomised clinical trial has been proven impractical and unrealistic. The heterogeneity of patients with varying degrees of coronary and carotid artery disease and the preference of carotid intervention are the main limitations for such a trial. Nevertheless, when conceived, such a trial should compare isolated CABG (including on and off pump surgery) with CAS-CABG and CEA-CABG in symptomatic and asymptomatic patients separately.
Optimal treatment of patients with concurrent carotid and coronary artery disease remains unresolved despite extensive publications during the last 30 years. Although only 40% to 50% of strokes after CABG are ipsilateral to an existing carotid lesion, carotid revascularization is one of the few available options to reduce the excessive stroke and death rates in patients with combined disease
Irreversible electroporation for cardiac ablation: from preclinical research to clinical application
No full textSingle pulse irreversible electroporation (IRE) is a promising alternative for thermal ablation techniques to perform cardiac ablation. With this technique, a direct current is applied between a multi-electrode circular catheter and an indifferent skin patch. Previous studies have shown its capability of creating sufficient lesions, without causing known complications as pulmonary vein stenosis and nerve-, oesophageal- and coronary artery damage.
In this thesis, we describe additional preclinical safety and feasibility aspects, as well as the first-in-human experience of single pulse IRE ablation for pulmonary vein isolation.
Chapter 2 describes the studies on the development of gaseous micro-emboli during
non-arcing 6-millisecond IRE-pulses in an in vitro bench experiment. Micro-bubbles
were visualized using high speed camera analysis and quantified using a bubble
counter. Subsequently, in chapter 3 we describe gas formation in an in vivo porcine
model, in which gas bubbles were visualized using transesophageal
echocardiography and quantified using a bubble counter which was attached to an
extracorporeal loop.
In chapter 4, the results of the FIM trial which was performed at the University
Medical Center Utrecht are described. In that study, 10 patients suffering from AF
underwent PVI using IRE ablation. The aim of this study was to investigate acute
safety and feasibility of IRE ablation to perform PVI. After that, a second study was
conducted in which several safety parameters were studied in a study population of
20 patients suffering from AF. The results of this study are described in chapter 5.
In order to further improve IRE ablation outcome, a novel method was developed to
determine electrode-tissue contact; the multi-electrode impedance measurements
system (MEIS). In chapter 6, we describe the results of a porcine study in which
the feasibility of MEIS to predict long term efficacy was studied, as well as the
preliminary experiences with MEIS during the FIM studies.
For future cardiac applications of IRE ablation, different catheter designs may be
more suitable. In chapter 7, we describe the feasibility of performing single pulse
IRE ablation using a multi-electrode linear catheter. In a porcine model, lesion size
was measured after epicardial ablation using a 7-electrode linear catheter. In
addition, chapter 8 describes a subsequent study on the feasibility of IRE ablation
using a linear catheter in the coronary sinus
Coronary Artery Disease: Inflammatory Pathways and Interventions
No full textCoronary artery disease remains one of the major causes of morbidity and mortality worldwide. Inflammation plays a crucial role in all stages of this disease. It is involved in the development of initial atherosclerotic lesions, plaque- progression, rupture and erosion, and additionally, contributes to ischemia and reperfusion injury after acute myocardial infarction. Therapeutic strategies that target the detrimental effects of the inflammatory process could therefore optimize current treatment regimens in patients with coronary artery disease. Recent landmark studies have finally brought anti-inflammatory therapy from theory to practice for secondary prevention. The road to clinical implementation of therapies that target the acute effects of inflammation in myocardial infarction, however, remains one with many hurdles. With this thesis we aimed to contribute to the unravelment of detrimental inflammatory pathways in the wide spectrum of coronary artery disease and investigated the effects and mechanisms of action of anti-inflammatory therapies, like a selective NLRP3 inflammasome inhibitor and colchicine. Furthermore, we studied the efficacy of the coronary sinus reducer in patients with refractory angina
Therapeutic strategies and prognosis in aortic coarctation: a lifelong disease
No full textAortic coarctation is a common but complex congenital heart condition, characterized by a narrowing of the proximal part of the descending aorta. Despite early surgical correction, the narrowing often recurs at a later age, which is frequently treated by stent implantation. In this thesis, the effectivity of stent implantation is evaluated and strategies for optimization of stent implantation are discussed, including epinephrine stress testing and aortic arch stenting. In the long term, patients with aortic coarctation are at increased risk of hypertension (in rest and/or during exercise) and consequent cardiovascular complications. This thesis provides insight into the occurrence of these complications and associated risk factors. A better understanding of the pathophysiology of cardiovascular morbidity and mortality in this patient population is needed to improve risk prediction and prevention
How to improve implantable cardioverter defibrillator therapy: Focus on patient-reported outcomes and enhanced programming
No full textCardiovascular implantable electronic devices (CIEDs), such as pacemakers, implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy (CRT) devices, have become the treatment of choice for cardiac rhythm disorders in subgroups of patients with heart disease. Due to the expanding indications for CIEDs and the availability of data supporting the clinical effectiveness of these devices, the number of CIED implants has increased significantly over the past decades. While in the past mortality reduction was the primary goal of CIED therapy, in recent years increasing attention has been paid towards assessing the impact of these life-saving devices on patients’ lives. Despite increased focus on the patient perspective, there are still several knowledge gaps that need to be filled in order to optimize the management and care for patients with a CIED. In the first two parts of the current dissertation, the course and determinants of patient-reported health status following CIED implantation and the impact of patient-reported outcomes (PROs) on prognosis in ICD and heart failure patients was explored. Findings indicate that levels of (disease-specific) health status vary considerably across subgroups of patients receiving an ICD or CRT-defibrillator device. Depending on the health status component that was measured, 4-7 different outcome trajectories were identified in the first 12-14 months after implantation. The different health status trajectories generally showed an initial small to large improvement between device implantation and short-term follow-up, followed by stabilization between short- and long-term follow-up. Overall, poorer health status was particularly associated with patients’ psychological profile (i.e., negative affectivity, anxiety, depression, use of psychotropic medication and Type D personality) and less with their clinical status (except for NYHA classification), which is consistent with earlier research. Furthermore, this dissertationcorroborates that PROs not only compromise the well-being of patients but also increase their risk of adverse clinical outcomes including premature death. In the third part of this dissertation, current and previous research on the effects of optimization of ICD programming on (unnecessary) ICD therapy and PROs was reviewed. In recent years, a series of important clinical trials have led to a shift in ICD programming towards less early and aggressive arrhythmia termination using in-device detection algorithms, prolonged detection duration, and no therapy delivery for slower and stable ventricular tachyarrhythmias, allowing them to terminate spontaneously. These efforts have significantly reduced the incidence of inappropriate ICD shocks (i.e., approximately 2% at 1-year). However, with respect to reducing appropriate but unnecessary antitachycardia pacing and shocks, there are still gains to be made. The ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life study (ENHANCED-ICD study), a prospective, single-arm safety monitoring study which was designed together with Tilburg University and implemented in the University Medical Center Utrecht, showed that programming a number of intervals to detectof 60/80 instead of 30/40 for ventricular tachyarrhythmia/ventricular fibrillation detection was safe for patients (N = 60) receiving a first-time ICD or CRT-defibrillator due to a primary or secondary prevention indication
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