CAPACITY

About 10% of the COVID-19 affected patients develop critical illness with a high mortality rate. This critical illness appears to be strongly linked with cardiovascular disease, as the prevalence of cardiovascular comorbidities and risk factors (such as diabetes and obesity) are often found among hospitalized COVID-19 patients. The consortium COVID@Heart believes that mitigating this cardiovascular burden of Covid-19 should start early, while patients are (still) outside the hospital. The Research COVID@Heart has three core activities: Develop a tool to identify high-risk cardiovascular patients with COVID-19 in a home environment, before the critical illness emerges. This tool will allow general practitioners to better notify high-risk patients, monitor them more closely (e.g. by using home saturation measurements), prescribe preventive cardiovascular medication earlier ('moon shot') and refer them to a hospital promptly when needed. Create a diagnostic tool to improve early differentiation between COVID-19 and a myocardial infarction, addressing the challenge of overlapping symptoms faced by general practitioners. Design a questionnaire supplemented by select biomarkers and blood tests to enhance the detection of cardiovascular disease in COVID-19 survivors experiencing prolonged symptoms of fatigue and shortness of breath, as these symptoms are potentially linked to accelerated subclinical cardiovascular disease. Origin Accurate information on how cardiovascular patients fared while still at home is lacking. This information is crucial to prevent hospital admissions. Therefore, COVID@HEART focuses on people who are not hospitalized but are at home and treated by their general practitioners. The Dutch Heart Foundation supports and funds this research into the best treatment for cardiovascular patients with a coronavirus infection.  

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.