Clinical evaluation of new methods for the assessment of heart failure

Although every physician seems to know the term "heart failure", there is no general agreement on its definition. Due to the complex nature of heart failure and the changing Insights into its pathophysiology over time, many different definitions exist. l.' Some focus on clinical presentations, while others highlight specific features of healt failure based on physiological concepts. In the studies which constitute this theSiS, the clinical definition of heart failure as proposed by the Task Force on Heart Failure of the European Sociery of Cardiology has been used.' In accordance with this definition patients were diagnosed as having heart failure when they had symptoms of heart failure, typically dyspnoea, fatigue or ankle swelling, and objective evidence of left ventricular dysfunction. This diagnosis was considered to be reinforced by an adequate response to treatment directed towards heart failure. It should be noted that patients with heart failure who have responded to treatment may be entirely asymptomatic. In the studies presented in this thesis, these patients were labelled as having asymptomatic left ventricular dysfunction. Several different adjectives can be used to describe heart failure. These include acute and chronic healt failure, congestive healt failure and systolic and diastolic healt failure. In its acute form, heart failure presents with rapidly developing symptoms and signs, such as dyspnoea, orthopnoea, pulmonary rates or peripheral oedema. Chronic heart failure, on the other hand, develops gradually, the symptoms are aspecific (e.g. fatigue) and the physical signs may be absent despite elevation of ventricular filling pressures.6 Since many patients with chronic healt failure who are treated with diuretics do not have physical signs of congestion, the term healt failure should be used instead of congestive heart failure. Although healt failure is often assumed to b

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice.

AIMS: Cardiac peptides have diagnostic and prognostic value in heart failure. Their plasma concentrations, however, are sensitive to rapid changes in haemodynamics. As blood sampling under standard conditions is not feasible in clinical practice, it is important to know which peptides are most resistant to change. Therefore, the present study investigated the differences in response to exercise between atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, brain natriuretic peptide and the recently identified N-terminal probrain natriuretic peptide.METHODS and RESULTS: Fifty-two patients with chronic heart failure performed a symptom-limited graded bicycle exercise. Blood samples for determination of plasma concentrations of cardiac peptides were drawn at rest and at peak exercise. There was a significant difference in percentage increase in response to exercise between the four peptides (P<0.0001). N-terminal proatrial natriuretic peptide increased less than atrial natriuretic peptide (5+/-18% vs 59+/-58%;P<0.0001). The difference in increase between N-terminal probrain natriuretic peptide and brain natriuretic peptide was less distinct but still significant (24+/-24% vs 38+/-52%, P<0.05). CONCLUSIONS: Both N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide increased less in response to exercise than their C-terminal counterparts. This implies that the circumstances under which blood sampling for measurements of N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide should be performed are more favourable than the blood sampling conditions for atrial natriuretic peptide and brain natriuretic peptide