Remote patient management of heart failure across the ejection fraction spectrum: A pre-specified analysis of the TIM-HF2 trial.

AIMS: The benefit of non-invasive remote patient management (RPM) for patients with heart failure (HF) has been demonstrated. We evaluated the effect of left ventricular ejection fraction (LVEF) on treatment outcomes in the TIM-HF2 (Telemedical Interventional Management in Heart Failure II; NCT01878630) randomized trial. METHODS AND RESULTS: TIM-HF2 was a prospective, randomized, multicentre trial investigating the effect of a structured RPM intervention versus usual care in patients who had been hospitalized for HF within 12 months before randomization. The primary endpoint was the percentage of days lost due to all-cause death or unplanned cardiovascular hospitalization. Key secondary endpoints were all-cause and cardiovascular mortality. Outcomes were assessed by LVEF in guideline-defined subgroups of ≤40% (HF with reduced EF [HFrEF]), 41-49% (HF with mildly reduced EF [HFmrEF]), and ≥50% (HF with preserved EF [HFpEF]). Out of 1538 participants, 818 (53%) had HFrEF, 224 (15%) had HFmrEF, and 496 (32%) had HFpEF. Within each LVEF subgroup, the primary endpoint was lower in the treatment group, i.e. the incidence rate ratio [IRR] remained below 1.0. Comparing intervention and control group, the percentage of days lost was 5.4% versus 7.6% for HFrEF (IRR 0.72, 95% confidence interval [CI] 0.54-0.97), 3.3% versus 5.9% for HFmrEF (IRR 0.85, 95% CI 0.48-1.50) and 4.7% versus 5.4% for HFpEF (IRR 0.93, 95% CI 0.64-1.36). No interaction between LVEF and the randomized group became apparent. All-cause and cardiovascular mortality were also reduced by RPM in each subgroup with hazard ratios <1.0 across the LVEF spectrum for both endpoints. CONCLUSION: In the clinical set-up deployed in the TIM-HF2 trial, RPM appeared effective irrespective of the LVEF-based HF phenotype.

Is 24/7 remote patient management in heart failure necessary? Results of the telemedical emergency service used in the TIM-HF and in the TIM-HF2 trials.

AIMS: Telemedical emergency services for heart failure (HF) patients are usually provided during business hours. However, many emergencies occur outside of business hours. This study evaluates if a 24/7 telemedical emergency service is needed for the remote management of high-risk HF patients. METHODS AND RESULTS: The study included 1119 patients merged from the TIM-HF and TIM-HF2 trials [age 69 ± 11, 73% male, left ventricular ejection fraction 37% ± 13, 557 New York Heart Association (NYHA) II/562 NYHA III]. Patients received a 24/7 physician-guided emergency service provided by the telemedical centre (TMC) in addition to remote management within business hours. During emergency calls, patient status, symptoms, electronic patient record, and instant telemonitoring data were evaluated by the TMC physician. Following diagnosis, patients were referred for hospital admission or instructed to stay at home. Apart from the TMC, patients could place a call to the public emergency service at any time. Seven hundred sixty-eight emergency calls were placed over 1383 patient years (0.56 calls/patient year). Five hundred twenty-six calls (69%) occurred outside business hours. There were 146 (19%) emergency calls for worsening HF, 297 (39%) other cardiovascular, and 325 (42%) non-cardiac causes, with a similar pattern inside and outside business hours. Of the 1119 patients, 417 (37%) placed at least one emergency call. Patients with NYHA Class III, higher N-terminal prohormone of brain natriuretic peptide (>1.400 pg/mL) levels, ischaemic aetiology of HF, implanted defibrillator, and impaired renal function had a higher probability of placing emergency calls. During study follow-up, patients who made an emergency call had a higher all-cause mortality (22% vs. 11%, P = 0.007 in TIM-HF; 16% vs. 4%, P < 0.001 in TIM-HF2) and more unplanned hospitalizations (324 vs. 162, P < 0.001 in TIM-HF; 545 vs. 180, P < 0.001 in TIM-HF2). Of the total 1,211 unplanned hospital admissions, 492 (41%) were initiated by a patient emergency call. Three hundred seventy-nine calls (49%) were placed to the TMC, whereas 389 calls (51%) were made to the public emergency service. Three hundred twenty-six (84%) of the calls to the public emergency service resulted in acute hospitalizations. The TMC initiated 202 (53%) hospital admissions; 177 (47%) patients were advised to stay at home. All patients that remained at home were alive during a prespecified safety period of 7 days post-call. Diagnoses made by the TMC physician were confirmed in 83% of cases by the hospital. CONCLUSION: A telemedical emergency service for high-risk HF patients is safe and should operate 24/7 to reduce unplanned hospitalizations. Emergency calls could be considered as a marker for higher morbidity and mortality.

Mortality and morbidity 1 year after stopping a remote patient management intervention: extended follow-up results from the telemedical interventional management in patients with heart failure II (TIM-HF2) randomised trial.

BACKGROUND: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial showed that, compared with usual care, a structured remote patient management (RPM) intervention done over 12-months reduced the percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause death. The aim of the study was to evaluate whether this clinical benefit seen for the RPM group during the initial 12 month follow-up of the TIM-HF2 trial would be sustained 1 year after stopping the RPM intervention. METHODS: TIM-HF2 was a prospective, randomised, multicentre trial done in 43 hospitals, 60 cardiology practices, and 87 general practitioners in Germany. Patients with heart failure, New York Heart Association functional class II or III, and who had been hospitalised for heart failure within 12 months before randomisation were randomly assigned to either the RPM intervention or usual care. At the final study visit (main trial), the RPM intervention was stopped and the 1 year extended follow-up period started, which lasted 1 year. The primary outcome was percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause mortality. Analyses were done using the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01878630. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1538 patients were enrolled (765 to the remote patient management group and 773 to the usual care group) in the main trial. 671 of 765 patients in the remote patient management group and 673 of 773 in the usual care group completed the main trial and started the extended follow-up period up to 1 year later. In the extended follow-up period, the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality did not differ significantly between groups weighted mean 5·95% [95% CI 4·59-7·31] in the RPM group vs 6·64% [95% CI 5·19-8·08] in the usual care group [rate ratio 0·79; 95% CI 0·78-1·21]). However, when data from the main trial and the extended follow-up period were combined, the percentage of days lost due to unplanned cardiovascular hospitalisation or all-cause death was significantly less in patients allocated to the RPM group (382 [50%] of 765; weighted mean 9·28%; 95% CI 7·76-10·81) than in the UC group (398 [51%] of 773; 11·78%; 95% CI 10·08-13·49; ratio of weighted average 0·79; 95% CI 0·62-1·00; p=0·0486). INTERPRETATION: The positive effect of our RPM intervention on morbidity and mortality over the course of the main trial was no longer observed 1 year after stopping the RPM intervention. However, because the TIM-HF2 trial was not powered to show significance during the extended follow-up period, our results are exploratory and require further research. FUNDING: German Federal Ministry of Education and Research.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.