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The cardio-renal syndrome (CRS) is an umbrella term for life-threatening diseases in which cardiac and renal dysfunction occur simultaneously. It has been shown that heart failure patients with an increase in intra-abdominal pressure and central venous pressure (CVP), indicating the presence of abdominal and venous congestion, have a higher risk to develop CRS due to worsening renal function. It is hypothesized that abdominal venous congestion impairs heart and kidney function by causing damage to the heart and kidneys. Abdominal venous congestion was induced via constriction of the thoracic vena cava inferior (VCI). The effect of this constriction on heart, kidney and liver function was followed-up for twelve weeks after surgery via different in vivo and in vitro experiments. It was shown that VCI constriction increased abdominal CVP, but that this increase had a limited effect on heart and kidney function. On the other hand, liver function deteriorated after VCI constriction. Therefore, it can be concluded that the rat model is validated as abdominal venous congestion was induced via constriction of the VCI. As the effect of VCI constriction on heart and kidney function was limited, the presence of abdominal venous congestion was insufficient to induce CRS. Consequently, in future CRS research, the role of abdominal venous congestion in CRS development and progression can be further explored by combining this rat model with other models of heart or kidney failure.

Diabetic cardiomyopathy (DCM) is a devastating disease of the heart, which increases the risk of heart failure in individuals with diabetes mellitus (DM). DCM is characterized by structural and functional changes of the myocardium, which are attributable only to the presence of DM and not to confounding factors or diseases. To date, little is known about the pathophysiology of this disease and there is no specific treatment available. Therefore, a clinically relevant animal model, in which DCM is developed after induction of DM, is warranted. This study showed that the combination of a high fat diet and a low dose of streptozotocin is efficient to induce type 2 diabetes, a deteriorated left ventricular relaxation and an increased left ventricular pressure in a rat model. Moreover, rats which are fed only a high fat diet, will develop the insulin resistance syndrome. This nongenetic rat model has the additional advantage of being easy to induce and can be used in the future to unravel the molecular mechanisms of DCM.

In case of an interatrial conduction delay (IACD), the left ventricle will contract before the left atrial contraction has ended and the mitral valve will close prematurely. This leads to left atrioventricular dyssynchrony. An IACD is frequent in pacemaker patients, but often neglected during follow-up. Therefore, the atrioventricular delay (AVD) will be left at nominal values which are usually too short. Consequently, these patients develop left atrioventricular dyssynchrony, causing dizziness, fatigue and dyspnoea. This could be prevented by lengthening the AVD. Otherwise, some of the patients have a too long AVD, leading to a suboptimal diastolic filling time. In these patients, the optimal AVD could be achieved by shortening the delay. Previous studies showed beneficial hemodynamic effects after AVD optimisation in cardiac resynchronisation therapy, biatrial and dual chamber pacemaker patients. We hypothesised that AVD optimisation would result in a better clinical outcome and left atrial function in dual chamber pacemaker patients. We set up a randomised cross-over study in which we optimised the AVD via transthoracic echocardiography (TTE). The benefit of optimisation was evaluated through an ergospirometry, a 6 minute walk test, TTE, HeartQoL questionnaire, NYHA class and BNP. Our study showed that individualised AVD optimisation by TTE improved the functional capacity and thus should be considered in every dual chamber pacemaker patient.

AGEs zijn eiwitten of vetten die in vivo versuikerd worden. Enerzijds is er steeds meer bewijs dat AGEs mogelijk ook betrokken zijn in de ontwikkeling en vooruitgang van hart- en nierfalen. Anderzijds is het bekend dat vrouwen over het algemeen minder gevoelig zijn aan cardiovasculaire aandoeningen. De huidige studie had als doel om het effect van AGEs op de hart- en nierfunctie en om de geslachtsverschillen in hart- en nierfunctie te bestuderen als gevolg van verhoogde AGEs in het lichaam. Mannelijke en vrouwelijke Sprague-Dawley ratten werden dagelijks i.p geïnjecteerd met AGEs (20 mg/kg) of BSA met eenzelfde concentratie gedurende 6 weken.Injecties van AGEs gedurende 6 weken leidden tot hart dysfunctie. Hypertrofie werd bevestigd met een verhoogd hart gewicht-tibia lengteverhouding in beide geslachten. Totaal collageen was hoger in AGE-BSA geïnjecteerde dieren, waarbij het totaal collageen hoger was bij mannen dan bij vrouwen. Urine analyse toonde veranderingen in elektrolyt concentraties van AGE-BSA behandelde mannelijke dieren en fibrose was uitgesproken in de cortex. Deze studie toont aan dat AGE-BSA injecties aanleiding geven tot fibrose in zowel het hartweefsel als nierweefsel. Mannelijke ratten vertonen meer uitgesproken fibrose dan de vrouwtjes wat de duidelijke verslechtering in hartfunctie in vivo deels verklaart.

HF is a complex clinical condition characterized by cardiac and non cardiac morbidity, with high morbidity and mortality and incremental costs for health care. The objective of this thesis was to investigate if optimal patient care through an individually tailored approach would lead to better outcomes. A first study was set up to assess the impact of RAS and ' blocker uptitration in HFrEF versus HFpEF patients after hospital admission; which concluded that uptitration of RAS blockers after a HF hospitalization is more feasible in younger patients with low co morbidity burden, and is an independent predictor of outcome in HFrEF but not HFpEF patients. Next to an optimal neurohumoral blocker therapy, elaborate HF care also comprises an extensive disease management program. A second study was set up to investigate the feasibility and impact of a hospital-wide, individually tailored and transmural disease management program in reducing ADHF and all-cause readmission rates and improving cl

Background: The novel urinary biomarkers for the early detection of kidney injury after ischemic or toxic insults have recently been well studied, including neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (Cys-C)and Nacetyl- β Dglucosaminidase (NAG). The lack of reference values have greatly impeded progress in the diagnosis and treatment of patients with AKI and have a detrimental effect on the possibly outcomes of clinical trials of cardiac surgery. Objective: The first objective of this study was to estimate the normal value of urinary NGAL, KIM-1, Cys-C and NAG in a healthy population. The second objective was to evaluate the diagnostic performance of urinary biomarkers in a prospective pilot study including adults after cardiopulmonary bypass (CPB) surgery. Methods: The age study population consist of 337 healthy non-smoking subjects (191 female, 146 male ranging from 4 months to 90 years). Urine samples were obtained at routine visit to the ZOL hospital. ELISA was used to measure urinary NGAL, KIM-1 and Cys-C. BIOQuant N-acetyl-B-D-Glucosaminidase (NAG) assay was used to measure NAG. The prospective pilot study consists of 25 adults (7 females, 18 males ranging from 51 to 84 years) who required CPB surgery. Urine and blood samples were obtained before and 3, 6, 12 and 24 hours after CPB surgery. Patients were divided into the AKI and non-AKI groups according to developed AKI after surgery, AKI was defined as a ≥ 0.3 mg/dl increase in sCr from the base line within 48h after the surgery. Urinary KIM-1 and NGAL were measured using ELISA assay. Results: Age study: significant age related differences were found for KIM-1, NGAL, Cys- C and NAG. In addition, significant differences between gender were found for KIM-1, NGAL and NAG. Cardiac study: 25 patients were enrolled, 20% developed AKI. Urinary KIM-1/Cr level was significantly increased 24h post surgery and was significantly associated with AKI within 24h ,while urinary NGAL level did not show such a performance. Conclusions: Based on our results, further study in larger population with biomarker panel is needed for the evaluation of normal values with variance factors as well as to establish the prediction value to diagnose AKI for long and short outcomes after cardiac surgery.