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Eur J Heart Fail. 2019 May 25. doi: 10.1002/ejhf.1530. [Epub ahead of print]

Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM-HF2 trial.

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Division of Emergency and Acute Medicine, Cardiovascular Process Research, Campus Mitte and Virchow, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Centre for Cardiovascular Telemedicine, Department of Cardiology and Angiology, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Cardiology (CVK) and Berlin Institute of Health, Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin Charité - Universitätsmedizin Berlin, Berlin, Germany.
Clinical Diagnostics, Thermo Fisher Scientific, Hennigsdorf, Germany.
Technical University Munich, Department of Prevention, Rehabilitation and Sports Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Department of Cardiology and Pneumology, Universitätsmedizin Göttingen, Göttingen, Germany.



The TIM-HF2 study showed less days lost due to unplanned cardiovascular hospitalization or all-cause death and improved survival in patients randomly assigned to remote patient management (RPM) instead of standard of care.


This substudy explored whether the biomarkers mid-regional pro-adrenomedullin (MR-proADM) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could be used to identify low-risk patients unlikely to benefit from RPM, thereby allowing more efficient allocation of the intervention. For 1538 patients of the trial (median age 73 years, interquartile range 64-78 years, 30% female), baseline biomarkers were used to select subpopulations recommended for RPM with various safety endpoints (100%, 98%, 95% sensitivity), and efficacy of RPM was assessed. Both biomarkers were strongly associated with events. The primary endpoint of lost days increased from 1.0% (1.4%) in the lowest to 17.3% (17.6%) in the highest quintile of NT-proBNP (MR-proADM). After combining biomarkers to identify patients recommended for RPM with 95% sensitivity, in the most efficient scenario (excluding 27% of patients; NT-proBNP < 413.7 pg/mL and MR-proADM < 0.75 nmol/L), the effect of RPM on patients was highly similar to the original trial (ratio of lost days: 0.78, hazard ratio for all-cause death: 0.68). Number needed to treat for all-cause death was lowered from 28 to 21. Rates of emergencies and telemedical efforts were significantly lower among patients not recommended for RPM. Biomarker guidance would have saved about 150 h effort/year per 100 patients of the eligible population.


The combined use of MR-proADM and NT-proBNP may allow safe, more precise, effective and cost-saving allocation of patients with heart failure to RPM and warrants further prospective studies.


Digital health; MR-proADM; NT-proBNP; Outcome; Remote patient management; Telemedicine


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