BACKGROUND AND AIMS: Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiovascular magnetic resonance (CMR) imaging and laboratory testing as central elements. STUDY DESIGN AND METHODOLOGY: The HERZCHECK trial is a prospective, randomized controlled trial employing a prospective randomized open blinded endpoint design. The study targets asymptomatic adults aged 40-69 years without a history of HF, but with at least one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, obesity, smoking/tobacco consumption, chronic diabetes mellitus, or chronic kidney disease. Participants undergo a comprehensive screening examination including a questionnaire-based medical history, laboratory testing, and CMR at baseline. Based on CMR-derived global longitudinal strain (GLS), participants are classified as stratum A (GLS <
-15%), B (GLS ≥ -15% to <
-11%), or C (GLS ≥ -11%), with strata B and C being defined as asymptomatic pre-HF. Ten percent of participants in stratum A and all of stratum B and C are subsequently randomized into two groups, receiving either conventional or innovative medical reports, the latter including information on GLS, guideline-based recommendations, and access to a lifestyle intervention app for cardiovascular prevention. Additionally, treating physicians of participants in the innovative group are granted access to an expert center for telemedical inquiries. Follow-up assessments are performed over 12 months to evaluate changes in GLS, as well as adverse cardiac events and quality of life. CONCLUSION: HERZCHECK aims to provide a blueprint for a comprehensive, contemporary screening approach tailored to the needs of the targeted structurally underserved population. By implementing this approach in a representative at-risk cohort, HERZCHECK will provide important new information about (a) the prevalence of asymptomatic pre-HF in at-risk patients and (b) the feasibility, added diagnostic value and health economic aspects of CMR exams as part of future screening mechanisms for HF in clinical routine care (NCT05122793).