PRECISE

Habitual physical activity is beneficial for cardiovascular health. Yet, many patients with cardiovascular disease are sedentary, and current physical activity programs often fail to achieve lasting improvements. At the extreme end of the activity spectrum, more athletes engage in long-term, high-volume, high-intensity training.  Emerging evidence suggests that there may be an upper limit of exercise for heart health and exceeding this threshold may attenuate the benefits of an active lifestyle. The FIT-HEART consortium seeks to develop tailored physical activity interventions for cardiovascular disease patients and to investigate safe exercise limits for recreational and elite athletes. The research FIT-HEART has three main goals: Co-create, implement and evaluate an innovative program that promotes physical activity by integrating incentives from the individual’s (social) environment tailored to the needs of specific subgroups, which can be seamlessly integrated into healthcare systems across the Netherlands, with potential for future expansion to other patient groups and the broader population. Assess the upper limits of exercise on heart health in recreational and professional athletes by conducting prospective studies in unique cohorts. This approach integrates extensive cardiac phenotyping, wearable monitoring, novel AI technologies, digital twinning, immunophenotyping, and long-term evaluation of clinical outcomes. Establish and expand a multidisciplinary, synergistic consortium focused on sports, exercise, and heart health. Our mission is to nurture young talent, foster innovative cross-domain collaborations, and secure funding for ongoing and future research. In partnership with end-users, we will disseminate outcomes to professionals, patients, and the public, while raising awareness of the wide-ranging health benefits of an active lifestyle. The origin The FIT-HEART consortium emerged from a shared ambition among academic institutions, healthcare partners, patient organizations, and policymakers to address sedentary lifestyles in cardiovascular disease patients and to investigate the cardiac effects of extreme exercise in both elite and recreational athletes. This interdisciplinary initiative builds upon prior collaborative research in sports cardiology, preventive medicine, and behavioral interventions aimed at promoting physical activity. FIT-HEART is well-aligned with the strategic agendas of the Dutch Heart Foundation and the Dutch CardioVascular Alliance (DCVA), both of which prioritize innovative solutions to reduce the burden of cardiovascular disease. By integrating incentives from people’s social environment, the consortium aims to create personalized treatment options that encourage lasting physical activity, while taking into account subgroup-specific needs. In parallel, the integration of advanced cardiovascular methodologies enables FIT-HEART to identify recreational and professional athletes at an early stage who are at risk for adverse cardiovascular health outcomes.

Digoxin is the oldest, market-authorized drug for heart failure (HF), and very cheap. A large trial with digoxin, the DIG trial, executed in the early nineties revealed a highly significant reduction in HF hospitalizations, but no effect on mortality. A post-hoc analysis of the DIG trial suggests that low serum concentrations of digoxin may not only improve HF hospitalizations but also mortality in chronic HF patients. To validate these findings, a prospective, randomized, placebo-controlled trial is required to redefine the role of digoxin in modern HF treatment. The Focus The primary objective of this study is to investigate whether low-level digoxin (targeting serum concentrations of 0.5-0.9 ng/mL), compared to a placebo, reduces (repeated) HF hospitalizations, (repeated) urgent HF hospital visits, and cardiovascular mortality when added to standard guideline-recommended therapies in chronic HF patients with reduced or mid-range ejection fractions (LVEF ≤50%). The Research This proposed trial is a national, multicenter, randomized, double-blind, placebo-controlled clinical trial involving 982 chronic HF patients aged ≥18 years, classified as NYHA II to ambulatory IV, LVEF ≤50%, and specific serum NT-proBNP concentrations based on rhythm and recent HF hospitalization status. Patients must also be on guideline-recommended therapies. The study population includes at least one-third with atrial fibrillation (AF) and one-third women to represent the real-life HF population. Patients were randomized to receive either a low-level digoxin or a placebo in a double-blinded manner. Digoxin Teva will be administered orally, starting at doses of 0.2mg or 0.1mg (based on age, renal function, and concomitant medication). No loading dose is given to the placebo group. After 4 weeks of evaluating medication (digoxin or placebo), concentrations will be measured. Dose adjustments will be made if needed to reach the target serum digoxin concentration range of 0.5-0.9ng/mL. The outcomes in reducing adverse cardiovascular events in patients with chronic heart failure of low-dose digoxin will be compared to the outcomes of the placebo. The origin This study was funded as part of the Dutch Heart Foundation's collaboration with the ZonMw GGG program on Good Use of Medicines (Goed Gebruik Geneesmiddelen) for better treatment of heart failure and atrial fibrillation, which was one of the 5 priority's that the Dutch Heart Foundation set in 2014. The DECISION study involves 38 hospitals and is led by cardiologists from UMC Groningen and the WCN.