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European Society of Cardiology guidelines for the treatment of heart failure (HF) prescribe uptitration of angiotensin-converting enzyme inhibitors (ACE-I) and β-blockers to the maximum-tolerated, evidence-based dose. Although HF prognosis can drastically improve when correctly implementing these guidelines, studies have shown that they are insufficiently implemented in clinical practice.
The aim of this study was to verify whether supplementing the usual care with the CardioCoach follow-up tool is feasible and safe, and whether the tool is more efficient in implementing the guideline recommendations for β-blocker and ACE-I.
A total of 25 HF patients were randomly assigned to either the usual care control group (n=10) or CardioCoach intervention group (n=15), and observed for 6 months. The CardioCoach follow-up tool is a two-way communication platform with decision support algorithms for semiautomatic remote medication uptitration. Remote monitoring sensors automatically transmit patient’s blood pressure, heart rate, and weight on a daily basis.
Patients’ satisfaction and adherence for medication intake (10,018/10,825, 92.55%) and vital sign measurements (4504/4758, 94.66%) were excellent. However, the number of technical issues that arose was large, with 831 phone contacts (median 41, IQR 32-65) in total. The semiautomatic remote uptitration was safe, as there were no adverse events and no false positive uptitration proposals. Although no significant differences were found between both groups, a higher number of patients were on guideline-recommended medication dose in both groups compared with previous reports.
The CardioCoach follow-up tool for remote uptitration is feasible and safe and was found to be efficient in facilitating information exchange between care providers, with high patient satisfaction and adherence.
ClinicalTrials.gov NCT03294811; https://clinicaltrials.gov/ct2/show/NCT03294811 (Archived by WebCite at http://www.webcitation.org/6xLiWVsgM)
Heart failure (HF) is a major health problem affecting more than 10% in the elderly over the age of 70 years [
Improvements in treatment strategies have reduced mortality and (re)hospitalization rates. In 2016, the updated guidelines of the European Society of Cardiology (ESC) concerning the diagnosis and treatment of acute and chronic HF with reduced ejection fraction were published [
The addition of remote monitoring combined with integrated clinical decision support in this aspect could provide added value for both the health care provider and the patient. Remote monitoring of vital parameters and other patient information could allow care givers to evaluate and adjust patients’ medication schemes remotely according to ESC guidelines [
The CardioCoach study combines a two-way communication platform with decision support algorithms together with remote monitoring sensors for active medication uptitration. The study will verify whether supplementing the guideline-driven usual care with this two-way communication platform can implement the guideline recommendations for β-blocker and ACE-I more efficiently. This paper focusses on the feasibility of the communication platform for adjusting HF medication remotely and for detecting early deterioration by monitoring blood pressure, heart rate, and weight changes. Patient’s vital measurements and therapy adherence were actively encouraged by the smartphone app and were evaluated together with the patient’s satisfaction of the CardioCoach tool.
This is a prospective single-center randomized control feasibility trial conducted in a Belgian tertiary care center (Jessa hospital, Hasselt, Belgium) with a specialized HF disease clinic. Newly diagnosed patients with HF and initiation of β-blocker and/or ACE-I therapy or patients with known HF but on suboptimal dosage of β-blocker and/or ACE-I therapy were approached. Upon inclusion, block randomization was used to divide patients in either the usual care control group or the CardioCoach intervention group (clinical trial registration with www.clinicaltrials.gov; identifier NCT03294811). All patients provided written informed consent and were followed for 6 months after study enrolment. The study complies with the Declaration of Helsinki, and the study protocol was approved by the local committee on human research.
ESC guidelines on uptitration of β-blocker and/or ACE-I therapy are primarily intended to be used by physicians. Therefore, medication dose adaptions were performed during occasional outpatient visits to the cardiologist or general practitioner. Medication doses were determined based on patient’s vital sign measurements, overall well-being, and symptoms. Besides an additional follow-up visit at 3 months, we did not modify the usual care as per standard practice organized in the institution where patients have a scheduled follow-up visit at 6 months.
Patients allocated to the CardioCoach intervention group also had a scheduled follow-up visit at 3 months and 6 months. For these patients, the usual care was supplemented with the CardioCoach follow-up tool to proactively uptitrate β-blocker and ACE-I treatment and improve medication adherence for β-blocker, ACE-I, and diuretic treatment. In terms of diuretic treatment, only medication adherence was monitored because it was not part of the active uptitration protocol. This intervention included a two-way communication platform connected to remote monitoring devices such as a weighing scale and blood pressure monitor to collect vital measurements (ie, weight, blood pressure, and heart rate), in which patients were followed by technical and clinical call centers. Medical follow-up (eg, medication uptitration, alerts on threshold crossing) was done by the clinical call center in the hospital, whereas technical follow-up (eg, missed transmissions, technical issues) was done by Remedus (Aartselaar, Belgium). Both call centers were active during working hours; notifications received during the weekend were read on Monday.
The two-way communication platform consisted of a smartphone with the preinstalled CardioCoach app, a blood pressure monitor, weighing scale, and a Web-based health management server (Remecare) with a clinical dashboard for the care provider (HF nurse). An overview of the CardioCoach follow-up tool can be found in
The CardioCoach app was used to trigger the patient to conduct different actions, such as record a vital sign measurement, complete a questionnaire, and confirm medication intake by sending reminders at predefined time points. For each action, a 5-hour time window was set in which the patient could record all necessary data. This time window could be customized for each patient and was made available an hour before and 4 hours after the ideal recording time. All vital sign measurements were transmitted automatically to the CardioCoach app without manual patient input. The patient-specific medication scheme for β-blocker, ACE-I, and diuretic treatment was automatically uploaded to the patients’ smartphones every morning to inform them about their actual medication dose for that day. When changes were applied to the medication scheme, the patient was notified via a pop-up message, which he/she had to confirm. In addition, a daily education tip was pushed by the smartphone app to the patient covering different HF disease aspects (eg, tips to manage fluid and salt restriction, exercise). Screenshots of the CardioCoach app are shown in
All information gathered via the CardioCoach smartphone app (ie, vital signs, questionnaires, medication intake) was automatically transmitted to a secured Web-based health management server (ie, Remecare) without patient input. On this server, the completeness of patient data and possible deviations of vital signs based on predefined thresholds were verified.
When a patient does not record medication intake or vital sign data or does not complete a questionnaire, a pop-up message was pushed 2 hours after the ideal recording time via the smartphone to inform the patient about the missed registration and stress the importance of this information for the medication uptitration process. If the patient still did not complete the required action 4 hours after the ideal recording time, a
In the CardioCoach intervention group, β-blocker and ACE-I medication uptitration was supported by a clinical decision support algorithm, initiated at study inclusion. The algorithm generated a medication uptitration proposal at fixed moments in time during the first 3 months of follow-up, known as the active uptitration phase. Moreover, every 2 weeks, the algorithm alternately generated a medication uptitration proposal for either the β-blocker or ACE-I.
Overview of the CardioCoach follow-up tool.
Vital sign thresholds.
Parameter | Thresholds for 3 consecutive days |
Weight | Baseline weight + 2 kg |
Heart rate | <60 bpma or >100 bpm |
Systolic blood pressure | <90 mm Hg or >160 mm Hg |
Diastolic blood pressure | <60 mm Hg or >95 mm Hg |
abpm: beats per minute.
Overview of the study protocol for both the CardioCoach intervention group and usual care control group. ACE-I: angiotensin-converting enzyme inhibitors; BW: blood withdrawal.
At the beginning of week 2, the first proposal was generated, which comprised β-blocker uptitration, followed by another proposal for ACE-I uptitration at week 4. In total, there were 6 uptitration proposals during the first 3 months. Before each proposal, the short version of the custom-made HF questionnaire (
Before implementation of the updated medication scheme on the patient’s smartphone app, every proposal of the algorithm was reviewed by a dedicated HF nurse. The nurse could either choose to confirm the proposal, to call the patient before taking a decision, to make other changes to the patient’s medication scheme or to leave it unchanged, or indicate that the optimal medication dose had been reached. During the last 3 months of follow-up (ie, from 3 to 6 months), the active uptitration algorithm was deactivated and was followed by a less intensive follow-up phase during which medication intake and vital sign parameters were still monitored and medication uptitration on the discretion of the HF nurse could still proceed.
Finally, at 6 months of follow-up, patients from the CardioCoach intervention group were provided with a CardioCoach user experience questionnaire to gain feedback on the use of the CardioCoach smartphone app, the remote monitoring sensors, the contact with HF nurses and technical follow-up team.
Maximum daily dose as recommended by European guidelines.
Active ingredient | Max daily dose (mg) | |
Perindopril | 10 | |
Enalapril | 10 | |
Ramipril | 10 | |
Lisinopril | 20 | |
Candesartan | 16 | |
Losartan | 100 | |
Bisoprolol | 10 | |
Nebivolol | 5 |
aACE-I: angiotensin-converting enzyme inhibitors.
Outcome measures included CardioCoach user experience, (therapeutic) adherence, call center statistics, algorithm performance, and the number of patients on guideline-recommended medication dose for β-blocker and ACE-I (
Demographic and functional characteristics were compared using descriptive statistics. Continuous variables were expressed as mean ± standard deviation if normally distributed, or otherwise as median (interquartile range, IQR). To define statistical differences between both groups, the independent samples student
In total, 25 patients were included in the CardioCoach study. One patient dropped out before 3 months of follow-up and was therefore excluded from analysis. After 3 months of follow-up, 2 more patients dropped out but were still included in the analysis until 3 months of follow-up, because they completed the active medication uptitration phase. The final study population consisted of 24 patients: 14 patients were included in the CardioCoach intervention group and 10 patients were included in the usual care control group. Baseline characteristics of the study population at the time of inclusion are provided in
On the basis of gathered data, the CardioCoach algorithm generated 72 medication uptitration proposals in total. In 7% (5/72) of the cases, the algorithm generated a conclusive proposal, whereas in 93% (67/72) of cases, the decision was left up to the HF nurse. This was mainly due to aberrant (67%, 48/72) or incomplete (25%, 18/72) data.
After each automatic uptitration proposal from the algorithm, the HF nurses in the clinical call center received a notification, which they had to consider. Nurses could respond in different ways to the uptitration proposal (
Overall, therapeutic adherence as confirmed by the patient via the smartphone app (8315/10,825, 76.81%) or via the technical call center after contacting the patient (1703/10,825, 15.73%) for the 3 drug treatments was 92.55% (10,018/10,825), with, respectively, 97.12% (3239/3335) for β-blockers, 94.89% (3549/3740) for ACE-I, and 86.13% (3230/3750) for diuretics. In 1 out of 5 cases, patients did not record medication intake into the CardioCoach smartphone app, and the technical call center had to contact the patients to verify medication intake (
Baseline characteristics of the study population at the moment of study inclusion (N=24). Continuous data are expressed as mean (SD) if normally distributed, and dichotomous data are expressed as n (%).
Variables | CardioCoach intervention group (n=14) | Usual care control group (n=10) | ||
Male gender, n (%) | 9 (64) | 6 (60) | >.99 | |
Age, years, mean (SD) | 63 (15) | 60 (15) | .55 | |
Body mass index, mean (SD) | 28 (5) | 28 (5) | .88 | |
Heart rate, mean (SD) | 73 (13) | 73 (13) | .99 | |
Systolic blood pressure, mean (SD) | 112 (14) | 127 (25) | .08 | |
Diastolic blood pressure, mean (SD) | 75 (12) | 75 (12) | .98 | |
New York Heart Association functional class (II/III), n (%) | 6 (43)/6 (43) | 4 (40)/5 (50) | .92 | |
Left ventricular ejection fraction percentage, mean (SD) | 28 (7) | 29 (7) | .84 | |
QRS width, ms, mean (IQRa) | 100 (90-121) | 100 (92-121) | .89 | |
Ischemic cardiomyopathy, n (%) | 4 (29) | 1 (10) | .36 | |
Dilated cardiomyopathy, n (%) | 5 (36) | 5 (50) | .68 | |
Obesity | 9 (64) | 3 (30) | .10 | |
Arterial hypertension | 9 (64) | 3 (30) | .10 | |
Smoking | 9 (64) | 9 (90) | .34 | |
Family history of cardiovascular diseases | 7 (50) | 4 (40) | .70 | |
Hypercholesterolemia | 9 (64) | 5 (50) | .68 | |
Chronic kidney disease | 2 (14) | 0 (0) | .49 | |
Atrial fibrillation | 6 (43) | 4 (40) | >.99 | |
Diabetes | 3 (21) | 1 (10) | .62 | |
Chronic obstructive pulmonary disease | 1 (7) | 1 (10) | >.99 | |
Pro-Brain Natriuretic Peptide, mean (IQR) | 559 (118-1278) | 262 (129-467) | .44 | |
Estimated glomerular filtration rat, mean (SD) | 50 (28) | 65 (19) | .16 | |
Angiotensin converting enzyme inhibitor | 7 (50) | 3 (30) | .42 | |
β-blocker | 7 (50) | 3 (30) | .42 | |
Spironolactone | 1 (7) | 1 (10) | >.99 | |
Loop diuretic | 1 (7) | 2 (20) | .39 | |
Statin | 7 (50) | 3 (30) | .42 | |
Calcium channel blockers | 0 (0) | 1 (10) | .42 | |
Antidiabetic medication | 1 (7) | 1 (10) | >.99 | |
Normal cell phone | 8 (57) | 6 (60) | >.99 | |
Smartphone | 3 (21) | 3 (30) | .67 | |
Computer at home | 7 (50) | 4 (40) | .70 | |
Internet connection at home | 2 (14) | 3 (30) | .62 | |
Tablet at home | 7 (50) | 4 (40) | .70 |
aIQR: interquartile range.
Overview of the different algorithm uptitration proposals and their frequency.
Type of uptitration proposal | Full sample (N=72), n (%) | β-blocker group (n=41), n (%) | ACE-Ia group (n=31), n (%) |
Uptitration to next level | 1 (1) | 1 (2) | 0 (0) |
No uptitration to next level | 4 (6) | 3 (7) | 1 (3) |
Uptitration dependent on evaluation by heart failure nurse, due to incomplete data | 18 (25) | 11 (27) | 7 (23) |
Uptitration dependent on evaluation by heart failure nurse, due to aberrant data | 48 (67) | 26 (63) | 22 (71) |
Uptitration dependent on evaluation by heart failure nurse, due aberrant blood parameters | 1 (1) | 0 (0) | 1 (3) |
aACE-I: angiotensin-converting enzyme inhibitors.
Overview of the different responses of the heart failure nurses to the algorithm uptitration proposals.
Response of nurses to uptitration proposal | Full sample (N=72), n (%) | β-blocker group (n=41), n (%) | ACE-Ia group (n=31), n (%) |
Confirm algorithm proposal | 50 (69) | 29 (71) | 21 (68) |
Patient was contacted before decision was made | 25 (35) | 17 (41) | 8 (26) |
Change of other medication | 10 (14) | 8 (20) | 2 (6) |
Optimal medication dose reached | 25 (36) | 13 (32) | 12 (39) |
aACE-I: angiotensin-converting enzyme inhibitors.
Therapeutic adherence for medication intake and vital sign measurement recording.
Therapeutic adherence | n (%) | ||
Confirm via smartphone | 8315 (76.81) | ||
Confirmed via Remedus | 1703 (15.73) | ||
Declined via smartphone | 351 (3.24) | ||
Declined via Remedus | 456 (4.21) | ||
Confirm via smartphone | 3902 (82.00) | ||
Confirmed via Remedus | 602 (12.65) | ||
No recording | 254 (5.34) |
For the 14 CardioCoach patients, the Remedus call center made 831 phone calls in total, with a median of 41 phone calls per patient (IQR 32-65). Phone calls were initiated in case of missed vital sign measurements (n=136), missed medication intake (n=661; diuretic intake 44.0% [291/661], ACE-I intake 34.9% [231/661], and β-blocker intake 21.0% [139/661]), or missing questionnaires (n=34). Due to the limited technical skills of the study participants, technical problems could hardly be solved remotely, and therefore, a device swap was performed in 10 patients: 4 patients had 1 device swap, 5 patients had 2 device swaps, and 1 patient had 3 device swaps.
Among the CardioCoach user experience questionnaire, 4 questionnaires were missing: 3 due to early study termination and 1 due to an issue with the Web-based questionnaire platform. Detailed results of these questionnaires can be found in
The number of patients on maximum daily dose as recommended by European Society of Cardiology guidelines for both β-blockers (left) and ACE-I (right). No significant differences were observed between both groups. ACE-I: angiotensin-converting enzyme inhibitors.
No significant differences were observed in the number of patients on guideline-recommended maximum β-blocker dose in the CardioCoach intervention group when compared with the usual care control group at both 3 months (43% vs 40%,
Additionally, in terms of ACE-I uptitration, no significant differences were observed at both 3 months (43% vs 40%,
Since 1997, ESC guidelines for the diagnosis and treatment of acute and chronic HF have recommended the optimization of drug treatment as the first step in patients diagnosed with HF [
The results of this feasibility study with 24 patients, monitored for a period of 6 months, showed a marginal increase in the number of patients on guideline-recommended β-blocker and ACE-I dose when using the CardioCoach remote monitoring follow-up tool compared with usual care alone. However, in comparison with previous studies, both our intervention and control group consisted of a higher number of patients, who were on guideline-recommended medication dose. Maggioni et al [
Feedback received from the patients using the CardioCoach follow-up tool revealed overall good patient satisfaction in terms of both the use of the remote monitoring devices and the contact between the patient and technical and clinical call centers. This resulted in excellent overall therapeutic adherence of the patients during the entire study period for medication intake (92.55%, 10,018/10,825) and vital sign measurements (94.66%, 4504/4758). In spite of the frequent reminders via the smartphone, the CardioCoach follow-up tool was well accepted by the patients as compared with remote monitoring strategies used in previous studies [
In this study, the algorithm was built with a large safety margin to avoid false positive uptitration proposals, which has led to a low number of conclusive proposal by the algorithm (7%, 5/72). In addition, every proposal had to be validated by a dedicated HF nurse. In 69% (50/72) of the cases, the HF nurse confirmed the algorithm proposal. This shows that parameter thresholds can be confined. In this sense, the current feasibility study was very useful for the future development and improvement of an optimal two-way communication system between patients and caregivers. On the basis of feedback from both patients and HF nurses, improvements can be made to the next generation, which will take into account the work efficiency of the HF nurses and enable a customized approach for patients (eg, patient-specific or less confined parameter thresholds, patient-specific uptitration scheme). The CardioCoach follow-up tool is very efficient in facilitating information exchange between the different care providers (ie, HF specialist, HF nurse, general practitioner, home nurse) and enables a safe way for medication uptitration, as there were no adverse events or false positive uptitration proposals reported. The use of the CardioCoach follow-up tool has been shown to be feasible when combined with a technical call center to handle technical issues and reduce the workload of the clinical call center. This study was unable to demonstrate a significant improvement of the CardioCoach follow-up tool on the number of patients on maximum guideline-recommended β-blocker and ACE-I dose. Probably, this is related to the fact that patients in the control group were also enrolled in a dedicated HF outpatient disease management program, where HF medication dosages were being optimized by intensive follow-up by specialized HF nurses and HF specialists. Hence, the CardioCoach follow-up tool might be more suitable in centers with less intensive HF disease management programs.
This feasibility study should be interpreted in the light of some limitations to place the study findings into a correct context. First, the small sample size and the single-center character may impact its external validity. Therefore, these results should be interpreted as hypothesis generating, and an additional multi-center study is necessary to confirm these results. In this study, the control group received the usual care as per standard practice organized in the institution and received no remote monitoring sensors. This is a general issue in multiple remote monitoring studies, which should be taken into account when interpreting study findings as relevant information from the control group may be missing. An alternative control group could be a group in the same setting (ie, with remote monitoring sensors), but without a physician reviewing the data. Next, technical improvements (eg, Bluetooth connectivity, battery autonomy) are necessary to improve the efficiency of the CardioCoach follow-up tool. Finally, the patient population used to conduct the feasibility study was recruited in a tertiary care center with a specialized HF clinic. Due to the high quality of the usual care provided (reflected by the high number of patients on maximum guideline-recommended medication dose in the usual care group compared with literature) with intensive outpatient follow-up, the institution under study may not have been the optimal choice to demonstrate a potential benefit of the CardioCoach follow-up tool on medication uptitration.
This study shows the feasibility and safety of a novel two-way communication platform with decision support algorithms in combination with remote monitoring sensors in implementing guideline recommendations concerning β-blocker and ACE-I uptitration. In addition, the CardioCoach follow-up tool was found to be efficient in facilitating information exchange and improving coordination among different care providers. Patients’ satisfaction was reported to be high, which has led to excellent adherence rates during a relative long follow-up period of 6 months. Many technical issues arose, clearly indicating the need for a technical call center. A larger multicenter randomized controlled trial needs to be conducted in centers with minimal usual care follow-up to assess the potential benefits of guideline-recommended medication dose.
Screenshots from the CardioCoach smartphone app with from top to bottom registration of medication intake, weight, blood pressure, and heart failure questionnaire.
Custom-made heart failure questionnaire pushed to the patient before an uptitration proposal or in case of aberrant vital sign data.
Detailed results of the CardioCoach user experience questionnaire (Part 1).
Detailed results of the CardioCoach user experience questionnaire (Part 2).
Detailed results of the CardioCoach user experience questionnaire (Part 3).
CONSORT‐EHEALTH checklist (V 1.6.1).
angiotensin-converting enzyme inhibitors
European Society of Cardiology
heart failure
interquartile range
This report is part of the Limburg Clinical Research Program UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. This study was conducted with financial support of Agentschap Innoveren en Ondernemen and supported by the local living lab Happy Aging. The authors thank the nursing staff of the clinical call center (M Houbrechts, H Goris, W Ceyssens, J Vercammen, L Jacobs, and N Geusens) and employees of Remedus (J Ravelingen and I Van Brussel) for their excellent support in the data collection.
None declared.