AbstractBackground

Self-care behaviour is important in avoiding hospitalization for patients with heart failure (HF) and refers to those activities performed with the intention of improving or restoring health and well-being, as well as treating or preventing disease. The purpose was to study the effects of a home-based mobile device on self-care behaviour and hospitalizations in a representative HF-population.

Methods and results

SMART-HF is a randomized controlled multi-centre clinical trial, where patients were randomized 1:1 to receive standard care (control group, CG) or intervention with a home-based tool designed to enhance self-care behaviour (intervention group, IG) and followed for 240 days. The tool educates the patient about HF, monitors objective and subjective symptoms and adjusts loop-diuretics. The primary outcome is self-care as measured by the European Heart Failure Self-care behaviour scale and the secondary outcome is HF related in-hospital days.

A total of 124 patients were recruited and 118 were included in the analyses (CG: n = 60, IG: n = 58). The mean age was 79 years, 39% were female, and 45% had an EF < 40%. Self-care was significantly improved in the IG compared to the CG (21.5 [13.25; 28] vs 26 [18; 29.75], p = 0.014). Patients in the IG spent significantly less time in the hospital admitted for HF (2,2 days less, RR: 0.48; 95% CI: 0.32 - 0.74; p = 0.001) .

Conclusion

The device significantly improved self-care behaviour and reduced in-hospital days in a relevant HF population.

IntroductionIn the context of heart failure (HF), self-care refers to activities performed with the intention of improving or restoring health and well-being, as well as treating or preventing the disease (1Strömberg A Jaarsma T Riegel B. ). It is widely understood that about 50% of HF hospitalizations are a direct consequence of inadequate self-care behaviour (2Stromberg A Martensson J Fridlund B Levin LA Karlsson JE Dahlstrom U. Nurse-led heart failure clinics improve survival and self-care behaviour in patients with heart failure: results from a prospective, randomised trial., 3Home monitoring heart failure care does not improve patient outcomes: looking beyond telephone-based disease management.). Trying to find means of enhancing the self-care behaviour of HF patients in order to reduce hospitalizations, is likely well worth the effort. Multidisciplinary HF-clinics including specialized heart-failure nurses where both titrating patients toward target doses according to guidelines, but also striving to improve patients’ self-care behaviour, have shown significant impacts on clinical outcomes (4Gandhi S Mosleh W Sharma UC Demers C Farkouh ME Schwalm J-D. Multidisciplinary heart failure clinics are associated with lower heart failure hospitalization and mortality: systematic review and meta-analysis., 5Savarese G Lund LH Dahlström U Strömberg A. Nurse-Led Heart Failure Clinics Are Associated With Reduced Mortality but Not Heart Failure Hospitalization.). Due to its resource efficiency relative to out-patient HF clinics, digital care and more specifically mHealth, i.e. medical and public health practice supported by mobile devices (6

WHO. mHealth: new horizons for health through mobile technologies. 2011 doi.

), could have an important role in enhancing self-care behaviour in this population (7Chib A van Velthoven MH Car J. mHealth Adoption in Low-Resource Environments: A Review of the Use of Mobile Healthcare in Developing Countries.).In spite of having great potential, research in the field of mHealth and HF has generally not been performed on patients that represent the general Swedish HF population, thus making generalizability of the findings low. A recent systematic review of mHealth HF research including more than 1 700 patients, report the mean age in published studies as 61 years (8Cajita MI Gleason KT Han HR. A Systematic Review of mHealth-Based Heart Failure Interventions.). Furthermore, 100% of the patients included, where ejection-fraction (EF) was reported, had heart failure with reduced ejection-fraction (HFrEF), i.e. EF 9Gerber Y Weston SA Redfield MM Chamberlain AM Manemann SM Jiang R Killian JM Roger VL. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010., 10Heiat A Gross CP Krumholz HM. Representation of the Elderly, Women, and Minorities in Heart Failure Clinical Trials.), HF with preserved ejection fraction (HFpEF) accounts for 50% of the HF population (11Parikh KS Sharma K Fiuzat M Surks HK George JT Honarpour N Depre C Desvigne-Nickens P Nkulikiyinka R Lewis GD Gomberg-Maitland M O'Connor CM Stockbridge N Califf RM Konstam MA Januzzi Jr., JL Solomon SD Borlaug BA Shah SJ Redfield MM Felker GM Heart Failure With Preserved Ejection Fraction Expert Panel Report: Current Controversies and Implications for Clinical Trials.) and approximately 50% of the HF patients are female (10Heiat A Gross CP Krumholz HM. Representation of the Elderly, Women, and Minorities in Heart Failure Clinical Trials.). The European Society of Cardiology (ESC) has put together an e-cardiology working group, which recently issued a position paper on challenges in digital health implementation in cardiovascular medicine, where they emphasize that any new e-solution must be designed for the population in question (12Frederix I Caiani EG Dendale P Anker S Bax J Bohm A Cowie M Crawford J de Groot N Dilaveris P Hansen T Koehler F Krstacic G Lambrinou E Lancellotti P Meier P Neubeck L Parati G Piotrowicz E Tubaro M van der Velde E. ESC e-Cardiology Working Group Position Paper: Overcoming challenges in digital health implementation in cardiovascular medicine.).

The purpose of this current study, called “Selfcare Management Intervention in Heart Failure” (SMART-HF), was to evaluate if a novel home-based mHealth tool could improve self-care behaviour and reduce HF-related in-hospital days in a population with more resemblance to the general Swedish HF-population, compared to previous research. This will allow for better assessment of the tool's suitability for implementation into clinical practice.

Methods Study design and population

SMART-HF was a multicentre, randomized controlled clinical trial (RCT), recruiting patients with HF from five primary care centres and two hospitals in southern Sweden in the county council Region of Skåne with a follow-up of eight months.

The study was approved by the regional ethics committee at Lund University, Sweden (protocol 2018/1, application nr 2017/956) and the research conducted conforms with the ethical principles of the Declaration of Helsinki. The study was registered at ClinicalTrials.gov with identifier: NCT03484286 before patient enrolment began.

Patients were eligible for inclusion if they had a diagnosis of HF according to the ESC guidelines (13Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ Falk V González-Juanatey JR Harjola VP Jankowska EA. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.), filled out the consent form, were considered able to handle the intervention by the recruiting health care professional (HCP) and had at least one acute hospital admission for HF within the past 12 months or according to the recruiting HCP after clinical assessment in risk of readmission. The clinical assessment was based on medical history, NYHA classification and levels of NT-proBNP.All recruited patients were listed at nurse-led out-patient HF clinics and all recruiting centres were connected to the Swedish Heart Failure Registry (SwedeHF, https://www.ucr.uu.se/rikssvikt-en/) assuring a standard of care throughout Sweden. According to centers’ protocol, three visits are the minimum scheduled outpatient visits during the first year of HF diagnosis and after that yearly visits. If unstable and/or in need of titration of medicines the recommendation is HF nurse visits every 2-3 weeks until stabilized. Both the control and intervention group were followed at out-patient HF clinics receiving the same standard of care.

Patients were assessed for eligibility by an HCP (physician or heart failure nurse) at the participating centre, either during a hospital admission or during an out-patient visit to the HF clinic at the primary care centre. The recruitment of patients was always made at an out-patient visit to ensure proper follow-up in both control and intervention group. After providing informed consent in writing, baseline data was collected at inclusion and after 8 months. Data collected was age, sex, weight, ejection fraction (EF), NYHA classification, blood pressure, heart rate, aetiology of HF, routine laboratory tests according to guidelines, comorbidities and drug therapy. The data was collected from the patient´s medical record, examination of the patient and questions to the patient and noted in a research case report form. The patient also filled out questionnaires about self-care behaviour and self-assessment of NYHA classification in person at a visit at the time of enrolment and after eight months. The EF was taken from the latest echocardiography examination available in the patients’ medical record. The research nurse provided sealed, opaque envelopes to each recruiting site. The responsible HCP at each site would then select an envelope from the batch of envelopes allotted to the centre in question and open it to see if the patient was to be included in the control group (CG) or the intervention group (IG). The randomization was performed locally at each site, 1:1 and the data analyst was blinded to participants allocation. Patients randomized to the IG had the intervention installed in their homes within seven days after randomization.

 InterventionThe patients in the intervention group were equipped with the home-based tool OPTILOGG (CareLigo AB, Sweden), a CE-marked class 1m medical device, at the earliest possible opportunity after the randomization. The patient received a home visit by a non-HCP technician who installed the tool and instructed the patient on how to use it. The tool is based on a tablet computer wirelessly connected to a weight scale and incorporates symptom monitoring, interactive education and adjustment of loop-diuretics in the patient´s home. When the tool is prescribed to a patient, the responsible physician inputs patient specific parameters to guide the flexible loop-diuretics regimen and after deployment it works as a closed-loop system. No monitoring activities by the HCPs are required after deployment, however, the trends can be shared with the HCP during a visit, at the patient's discretion. The patient is encouraged to use the tool daily, and daily use involves registering weight, getting today´s dose of loop-diuretics and a brief education about living with HF. Every five days the patient is asked to assess his/her symptoms on an ordinal scale on the screen. The tool thus supports the patient in exercising self-care, addressing maintenance, monitoring and management, the three main components of self-care in the context of chronic illness (14Riegel B Jaarsma T Stromberg A. A middle-range theory of self-care of chronic illness.). If the tool detects a deterioration in HF status, the patient is encouraged to contact his/her HCP. The same telephone number that the IG patients were encouraged to call by the tool in case of deterioration in HF status was also provided to the CG patients. The company providing the technology provided technical support via telephone during office hours. OutcomesThe primary outcome was self-care behaviour measured by the European Heart Failure Self-care behaviour scale (EHFScB-9), a valid and reliable instrument (15Jaarsma T Arestedt KF Martensson J Dracup K Stromberg A. The European Heart Failure Self-care Behaviour scale revised into a nine-item scale (EHFScB-9): a reliable and valid international instrument.). It consists of nine questions, each with five possible answers on an ordinal scale. The output ranges from 9 to 45, where a lower score denotes better self-care behaviour and reduces the risk of adverse clinical outcomes (16

Kato N, Kinugawa K, Nakayama E, Tsuji T, Kumagai Y, Imamura T, Maki H, Shiga T, Hatano M, Yao AJIhj. Insufficient self-care is an independent risk factor for adverse clinical outcomes in Japanese patients with heart failure. 2013;54(6):382-9. doi: 10.1536/ihj.54.382.

). The outcome was measured at baseline and after 240 days.

The secondary outcome was the number of in-hospital days due to HF after 240 days of intervention.

Other outcome measures were event-free survival, defined as the composite end-point of time to the first occurrence of HF-related emergency room (ER) visit, HF-admission or death, a recommended end-point for clinical studies in HF (17Hicks KA Mahaffey KW Mehran R Nissen SE Wiviott SD Dunn B Solomon SD Marler JR Teerlink JR Farb A Morrow DA Targum SL Sila CA Hai MTT Jaff MR Joffe HV Cutlip DE Desai AS Lewis EF Gibson CM Landray MJ Lincoff AM White CJ Brooks SS Rosenfield K Domanski MJ Lansky AJ McMurray JJV Tcheng JE Steinhubl SR Burton P Mauri L O'Connor CM Pfeffer MA Hung HMJ Stockbridge NL Chaitman BR Temple RJ 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.), as well as unplanned hospital visits due to HF after 240 days of intervention.We also analysed system adherence to the tool that was defined as the number of days the patient used the tool (reading information, reporting symptoms or weighing themselves), divided by the number of days the patient has been equipped with it (15Jaarsma T Arestedt KF Martensson J Dracup K Stromberg A. The European Heart Failure Self-care Behaviour scale revised into a nine-item scale (EHFScB-9): a reliable and valid international instrument.). No adjustments were made if the patient was admitted and therefore was not able to use the tool.

All hospitalizations and ER visits during the follow-up time were adjudicated as being HF-related or not, based on the diagnosis code (ICD-10 I.50) in the medical records.

 Sample size and statistical analysesThe primary and secondary null-hypothesis were that there is no difference in self-care behaviour, or in-hospital days between the CG and the IG after 240 days, respectively. We employed the method to estimate sample-size proposed by Li et al. (18Li H Wang L Wei L Quan H. Sample size calculation for count data in comparative clinical trials with nonuniform patient accrual and early dropout.), which was also used in the study by Hovland-Tånneryd et al. (19Hovland-Tanneryd A Melin M Hagglund E Hagerman I Persson HE. From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials.). Since this current study sought to recruit older and thereby likely sicker patients, we assumed a 15% higher event-rate overall than in the paper by Hovland-Tånneryd et al., and an effect size of 40% since the duration of the current study was one third longer than the previous studies. This yielded a sample size equal to 58 + 58 patients in order to reject the primary and secondary null hypothesis with 80% power. With an estimated drop-out rate of 5%, the target for enrolment was set at 124 patients.

Baseline characteristics were analysed using the χ2 test and a t-test for independent samples for categorical, and continuous and normally distributed variables respectively. The selfcare behaviour (EHFScB-9 score) being ordinal and non-normally distributed data, was analysed using the Mann-Whitney U test. In-hospital days and unplanned hospital visits were modelled as over-dispersed count data and analysed using negative binomial regression. Adjusted and unadjusted Cox proportional hazards modelling was used to analyse event-free survival. The covariates included in any adjusted models, are those covariates where a significant difference between the CG and IG was detected post-randomization. The effect on adherence to the tool by different factors was analysed with multiple linear regression. P-values of less than 0.05 were considered statistically significant and all significance tests were two-tailed. The analyses were performed in accordance with a modified intention-to-treat principle on the full analysis set, consisting of all randomised patients who gave consent and began their assigned care. Specifically, all patients in the IG equipped with the tool were included in the analysis, irrespective if they decided to return the tool or stop using it prior to the 240-day follow-up. All statistical calculations were performed in IBM SPSS Statistics 25.

Discussion

An eight-month intervention with the mHealth tool improved self-care behaviour by 21% and reduced HF related in-hospital days by 52%, corresponding to 2.2 days per patient. Furthermore, it led to a 50% reduction in the risk of HF-event or death.

The recruited patients from the southernmost part of Sweden are a good representation of HF patients in terms of co-morbidities, aetiology, type of HF (i.e. HFrEF, HFmrEF and HFpEF), age and gender distribution, both in the general Swedish population (9Gerber Y Weston SA Redfield MM Chamberlain AM Manemann SM Jiang R Killian JM Roger VL. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010.) and for hospitalized patients (20Edvinsson ML Stenberg A Astrom-Olsson K. Improved outcome with standardized plan for clinical management of acute decompensated chronic heart failure.), except for patients in NYHA-class IV. All patients were followed up at nurse-led out-patient HF clinics and appear to be well treated with 86% on RAAS-blockade and 92% on beta-blockers.The self-care behaviour was improved by 4.5 points or 21%, which is similar to what has been published by others, where an intervention led to improvements by 3 (2Stromberg A Martensson J Fridlund B Levin LA Karlsson JE Dahlstrom U. Nurse-led heart failure clinics improve survival and self-care behaviour in patients with heart failure: results from a prospective, randomised trial., 21Köberich S Glattacker M Jaarsma T Lohrmann C Dassen T. Validity and reliability of the German version of the 9-item European Heart Failure Self-care Behaviour Scale.) and 4 (22Peters-Klimm F Campbell S Hermann K Kunz CU Muller-Tasch T Szecsenyi J Competence Network Heart F. Case management for patients with chronic systolic heart failure in primary care: the HICMan exploratory randomised controlled trial.) points. However, larger improvements have also been published with 8 points improvement, including the previous studies of this mHealth tool (19Hovland-Tanneryd A Melin M Hagglund E Hagerman I Persson HE. From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials., 23Pulignano G Del Sindaco D Minardi G Tarantini L Cioffi G Bernardi L Di Biagio D Leonetti S Giovannini E. Translation and validation of the Italian version of the European Heart Failure Self-care Behaviour Scale.). One of the reasons we didn't see a larger improvement could be that the patients in this study had already received education at the HF clinics.In the meta-analysis by Hovland-Tånneryd et al. where two studies of the same intervention as in our study were analysed, they report 33% and 28% reductions of in-hospital days due to HF after six months for the two included studies respectively, and an adjusted total reduction based on analysing both studies of 29.2% or 1.8 days per patient (19Hovland-Tanneryd A Melin M Hagglund E Hagerman I Persson HE. From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials.). The absolute reduction is similar to ours, but the relative reduction was larger in our material. This discrepancy might by explained by the fact that none of the patients in the study by Melin et al. had attended a HF clinic, and therefore were less well treated, with the result being more in-hospital days in their material, thereby reducing the relative reduction (24Melin M Hagglund E Ullman B Persson H Hagerman I. Effects of a Tablet Computer on Self-care, Quality of Life, and Knowledge: A Randomized Clinical Trial.).An intervention consisting of a weight- and symptom diary, flexible diuretics and education sessions (i.e. very similar to the investigated intervention) by Cline et al. reported a 49% reduction in hospital days. The population investigated was similar to ours, in that the mean age was 76 and 47% were female (25Cline CM Israelsson BY Willenheimer RB Broms K Erhardt LR. Cost effective management programme for heart failure reduces hospitalisation.). McAlister et al. published a meta-analysis of similar interventions, where they report a 43% reduction in HF hospitalizations based on data from 20 studies (26McAlister FA Stewart S Ferrua S McMurray JJ. Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials.).This is the first study on this mHealth tool in which a significant improvement in event-free survival as well as a significant reduction in unplanned hospital visits due to HF is reported. It would be interesting to further explore and confirm these specific outcomes in future studies. The effects on the outcomes relating to hospitalizations and in-hospital care are likely the consequence of three different modes of action of the intervention. The first is the significantly improved self-care behaviour, which leads to the patient needing less care (27Kato N Kinugawa K Nakayama E Tsuji T Kumagai Y Hatano M Yao A Jaarsma T Komuro I Nagai R. Insufficient self-care is an independent risk factor for cardiac events in Japanese patients with heart failure: a 2-year follow-up study.). The second mode is that the flexible diuretics regimen can attenuate the effects of sudden weight gains, which in other RCTs has shown to reduce hospitalizations by approximately 50% (28DeWalt DA Malone RM Bryant ME Kosnar MC Corr KE Rothman RL Sueta CA Pignone MP. A heart failure self-management program for patients of all literacy levels: a randomized, controlled trial., 29Prasun MA Kocheril AG Klass PH Dunlap SH Piano MR. The effects of a sliding scale diuretic titration protocol in patients with heart failure.). It has previously been published that only a minority of patients adhere to weight based flexible diuretics, even after a recent hospitalization (30Lainščak M Cleland JG Lenzen MJ Nabb S Keber I Follath F Komajda M Swedberg K. Recall of lifestyle advice in patients recently hospitalised with heart failure: a EuroHeart Failure Survey analysis.), whereas the investigated tool managed to return the weight back to normal after sudden weight gains in 59% of the cases in this study. The third mode is that when the improved self-care behaviour is not enough, the tool detects the deterioration in HF status and encourages the patient to seek care. This means that the patient will contact the HCP at an earlier stage of the deterioration, and a planned visit can be scheduled. Furthermore, it is common that patients misunderstand their drug regimens (31van der Wal MH Jaarsma T Moser DK van Gilst WH van Veldhuisen DJ. Qualitative examination of compliance in heart failure patients in The Netherlands.) and since the mHealth tool increases knowledge about HF (24Melin M Hagglund E Ullman B Persson H Hagerman I. Effects of a Tablet Computer on Self-care, Quality of Life, and Knowledge: A Randomized Clinical Trial.), and also significantly enhances self-care behaviour where drug compliance is one constituent, it is conceivable that the IG displayed improved adherence to pharmacological therapy, which also should positively influence outcomes. This will be investigated further in future studies.Lastly, the adherence to the mHealth tool was an 85% median adherence after eight months. The adherence at six months was 92%, which is similar to previous data indicating an adherence to the same tool of 94% at six months (19Hovland-Tanneryd A Melin M Hagglund E Hagerman I Persson HE. From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials.). These numbers are high, especially since the HCPs are not involved and do not actively encourage patients to use the tool once deployed. A qualitative study has reported that the investigated tool is easy to use and understand (32Hägglund E Strömberg A Hagerman I Lyngå P. Theory Testing of Patient Perspectives Using a Mobile Health Technology System in Heart Failure Self-care.).

The results from SMART-HF are very similar to previously published results from studies of the same mHealth tool. The population studied is a good representation of the general Swedish HF population, and it is reasonable to assume that these findings should translate well to a general setting of HF care.

 Methodological issuesThe study size is limited, which should be considered when interpreting the results as the risk of a Type I error increases with a small sample size. However, appropriate sample-size calculations were performed a priori. The results might add the most value when interpreted together with the other two studies investigating the same intervention (19Hovland-Tanneryd A Melin M Hagglund E Hagerman I Persson HE. From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials., 24Melin M Hagglund E Ullman B Persson H Hagerman I. Effects of a Tablet Computer on Self-care, Quality of Life, and Knowledge: A Randomized Clinical Trial.).

Due to the nature of the intervention, placebo-control was not possible. The mitigator for this was to provide all patients in the CG with the same contact phone number as the mHealth tool presents to patients in the IG and the instruction to call in case of worsening symptoms. Due to one inclusion criterion being clinical assessment, it is possible that some healthier HF patients with lower risk of admission were included in the study.

There were patients excluded from the analysis post-randomization, and all had an EF>40% and a hypertensive HF aetiology. However, the two study arms were still balanced with regards to these characteristics, and the excluded patients from the CG were not different from the patients excluded from the IG. We employed the same approach to define the final analysis data set as in the TIM-HF2 study, published in the Lancet in 2018 (33Koehler F Koehler K Deckwart O Prescher S Wegscheider K Kirwan BA Winkler S Vettorazzi E Bruch L Oeff M Zugck C Doerr G Naegele H Stork S Butter C Sechtem U Angermann C Gola G Prondzinsky R Edelmann F Spethmann S Schellong SM Schulze PC Bauersachs J Wellge B Schoebel C Tajsic M Dreger H Anker SD Stangl K. Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial.).In spite of randomization, there was significantly worse kidney function (as measured by eGFR) and a higher prevalence of diabetes mellitus in the IG. The patients in the IG also reported more severe symptoms than what was assessed by the HCP in terms of NYHA-class. These conditions (diabetes,