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Abstract
Background Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is now the standard of care, but whether the demonstrated benefits of RM translate into improvements in heart failure (HF) management is controversial. This systematic review addresses the role of RM in patients with HF with a CIED.
Methods and results A systematic search of the literature for randomised clinical trials in patients with HF and a CIED assessing efficacy/effectiveness of RM was performed using MEDLINE, PubMed and Embase. Meta-analysis was performed on the effects of RM of CIEDs in patients with HF on mortality and readmissions. Effects on implantable cardiac defibrillator (ICD) therapy, healthcare costs and clinic presentations were also assessed.
607 articles were identified and refined to 10 studies with a total of 6579 patients. Implementation of RM was not uniform with substantial variation in methodology across the studies. There was no reduction in mortality or hospital readmission rates, while ICD therapy findings were inconsistent. There was a reduction in patient-associated healthcare costs and reduction in healthcare presentations.
Conclusion RM for patients with CIEDs and HF was not uniformly performed. As currently implemented, RM does not provide a benefit on overall mortality or the key metric of HF readmission. It does provide a reduction in healthcare costs and healthcare presentations.
PROSPERO REGISTRATION NUMBER CRD42019129270.
- heart failure
- arrhythmias, cardiac
- cardiomyopathies
- pacemaker, artificial
Data availability statement
Data are available upon reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is the standard of care. While this improves management of these devices, how this contributes to the management of heart failure (HF) is unclear.
WHAT THIS STUDY ADDS
RM of CIEDs does not improve the management of patients with HF.
In patients with HF who have a CIED, the utility of RM and its role with respect to HF is poorly defined.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
RM requires further refinement and investigation before it can be recommended routinely for patients with HF and CIED.
Introduction
Despite substantial improvements in the treatment of heart failure (HF), contemporary studies show that the 1-year mortality for patients with HF remains at 20%–30% post hospital admission.1–3 Cardiac implantable electronic devices (CIEDs) have evolved in their role in the management patients with HF. Implantable cardiac defibrillators (ICDs) provide protection against sudden cardiac death. Cardiac resynchronisation therapy (CRT) reduces mortality and improves quality of life. More recently, remote monitoring (RM) provides the ability to collect regular detailed data about cardiac function and rhythms. These data from CIEDs may include measurement of resting heart rate, patient activity level, heart rate variability, respiratory rate, heart sound intensity and intrathoracic impedance. Thus far, studies using these data to improve patient risk stratification have not shown benefit.4
RM for CIEDs is the ‘automated transmission of data based on pre-specified alerts related to device functionality and clinical events’.5 The use of RM for patients with a CIED carries a class 1A recommendation5; however, major guidelines are unclear on their recommendations for how RM should be used in patients with HF and a CIED.
A previous work published in 2015 focused on the use of RM on the management of ICDs and did not show a mortality benefit. Since that review, several large studies have contributed to our understanding.6
In this review, we sought to bring together data from all randomised clinical trials involving RM with a CIED in patients who have HF and examine the effects of RM on outcomes, including mortality, HF readmission, device therapies, health economics and the use of outpatient clinic visits.
Methods
This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.7 The protocol was prospectively registered with the International Prospective Register of Systematic Reviews (registration number CRD42019129270).
Data sources and searches
Databases PubMed, MEDLINE and Embase were searched from January 1990 to February 2019. The search terms used were those associated with CIEDs (Permanent Pacemaker, ICD, CRT) HF and RM (home monitoring). The bibliographies of all relevant studies were searched for by the authors for additional relevant articles. The search was restricted to English language and human subjects. See Search strategy, online supplemental appendix 1.
Supplemental material
Study selection
Studies were eligible if (1) they were randomised controlled trials; (2) they included adults (≥18 years) with a confirmed diagnosis of HF, including both preserved and reduced systolic functions according to diagnostic methods; (3) subjects had a CIED that was subject to RM; (4) they compared RM of CIEDs to control (CIEDs without RM); and (5) they reported one or more of the following primary outcome measurements: mortality (all-cause and HF-related), hospitalisation (all-cause or HF-related hospitalisation) or the following secondary outcome measurements: device therapies, health economics or reduction in outpatient clinic visits.
Data extraction and risk of bias assessment
Data were extracted using a customised template for this study. Data extracted included the number of patients, age, sex, duration of the study, type of CIED devices, ejection fraction, use of HF medication, QRS measurements, New York Heart Association classification, mortality and HF readmission data. Data pertaining to device therapy and economic assessment were also recorded.
Study risk of bias was assessed using Cochrane standard criteria.7 Study selection, data extraction and risk of bias assessment were carried out independently by two authors (MM and MR). Abstracts of the papers identified by title in the initial search were evaluated by two authors (MM and MR) for appropriateness to the study question. Full-text articles of all potentially relevant papers were obtained and evaluated in detail. Articles were assessed independently by two authors against the eligibility criteria. Any disagreements were resolved by consensus, and decisions were independently checked by a third author (AS).
Statistical analysis
Summary statistics from the individual studies were used as patient-level data were not available. Included studies were grouped according to primary outcome data (mortality and HF readmission) and a pooled unadjusted risk of 12-month mortality and 12-month HF readmission was obtained where relevant data were available. Studies were weighted according to their size in the pooled analysis.
We used a fixed effects model to pool results across studies. Estimates of heterogeneity are reported as the I2 statistic (where I2 of >50% was assumed to be a result of significant heterogeneity) and are presented together with the test of statistical significance.
Meta-analysis of the outcomes was conducted using ‘Metan’ function. All analyses were undertaken using Stata V.15.1.
Results
Summary measures and synthesis of results
A total of 607 articles were identified in the literature search. Three hunded sixty-one duplicates were removed, and subsequently, 246 studies were screened for inclusion. This resulted in removal of 200 studies after abstract review and 46 full-text studies assessed for eligibility. Thirty-five full-text studies were excluded according to the predefined inclusion criteria for study design (n=18), previously unidentified duplicate studies (n=5), lack of HF outcomes (n=7), lack of remote or home monitoring (n=2), intervention type (n=2) and patient population (n=1). Eleven studies were included in the final review. This process is summarised in the Consolidated Standards of Reporting Trials diagram (figure 1; online supplemental file 2).
Supplemental material
Consolidated Standards of Reporting Trials diagram.
Risk of bias
The risk of bias was assessed for 11 studies using the Cochrane Collaboration Tool.7 One study was deemed to be at high overall risk of bias due to incomplete outcome data, underpowered for the study question and was therefore excluded. Ten studies were included in the final analysis.8 All other studies were deemed to have low to moderate risk of bias. The most common reason for moderate overall risk of bias was inability to blind participants and study personnel from RM.
Study characteristics
The characteristics of the included studies are summarised in table 1. Follow-up duration was between 12 months and 34 months. All studies included patients with both ICDs and CRT devices. No study included patients with single-chamber or dual-chamber pacemakers. All studies reported systolic function, and the average ejection fraction for all studies was between 23% and 35%. All studies reported New York Heart Association class and were predominately classes II and III. Cardiovascular medications were reported in nine studies. There was significant variation in standard of care between studies, ranging between 3 monthly and 6 monthly reviews or follow-up at physicians’ discretion.
Summary of studies included in this systematic review and mata-analysis
Mortality outcomes were reported in nine studies, and data on 12-month mortality were available for eight studies. Admission for HF (including readmission) was reported at 12 months for seven studies. In total, 6579 patients are represented in these 10 studies with 3045 in the control arms and 3534 in the RM arms.
Primary outcome
Effect of RM on mortality
Nine studies reported mortality.9–17 One study was excluded from the pooled analysis as 12-month outcomes were not reported.17 Eight studies were assessed for 12-month mortality outcomes, representing 6106 total patients with 3295 patients in the active arms and 2811 in the control arms. At 12 months, there was no significant difference in mortality with a total of 218 deaths in the active arms and 213 deaths in the treatment arms. Four studies reported mortality outcomes beyond 24 months,9 10 15 17 with the longest mean follow-up period being 34 months, and in these studies, there was also no difference in mortality between the groups. Only one study demonstrated a statistically significant reduction in mortality (3.0% vs 8.2%, p value 0.004).12
Pooled outcomes for the unadjusted 12-month mortality of the eight studies were negative with a relative risk of 1.02 (95% CI 0.85 to 1.23, p=0.055, I2=49.2%) (figure 2).
Twelve-month mortality, the value for the I2 statistic and p value associated with the heterogeneity Q test are shown in parentheses for each overall total.
Effect of RM on HF readmissions
Seven studies reported HF admission or readmission outcomes, representing a total of 4767 patients with 2387 patients in the active arms and 2380 in the control arms.9–15 While follow-up duration was variable (12–34 months), all seven studies reported HF admission outcomes at 12 months: these were similar in both groups (592 events in the active arms and 551 events in the control arms). Only one study demonstrated reduced risk of presentation for worsening HF in the RM arm,13 with the remaining six studies reporting no difference.
Pooled outcome analysis for unadjusted 12-month HF readmission including patients from all seven studies showed no difference between RM and control arms with a relative risk of 1.07 (95% CI 0.97 to 1.20, p=0.658, I2=0.0%) (figure 3).
Twelve-month heart failure readmission, the value for the I2 statistic and the p value associated with the heterogeneity Q test are shown in parentheses for each overall total.
Secondary outcomes
Effect of RM on ICD therapy
Three studies reported ICD therapy outcomes representing 849 patients in total.11 14 17 Two studies11 14 documented no difference between the active and control arms. The Effectiveness and Cost of ICDs Follow-up Schedule with Telecardiology (ECOST) study17 demonstrated a reduction in inappropriate and appropriate shocks in the RM group compared with the standard care group. In the ECOST study, there were a total of 193 shocks in the active arm and 657 in the control arm (p valve of 0.02). Of the delivered therapy, 11 patients (28 total shocks) in the active arm, and 22 patients (283 total shocks) in the control arm received inappropriate shocks (p value of 0.03).
Economic analysis
Two studies, representing 1065 patients, reported economic outcomes.10 18 An economic analysis of the Evolution of Management Strategies of Heart Failure Patients With Implantable Defibrillators (EVOLVO) was performed by Zanaboni et al.18 The principal finding was that RM reduced associated healthcare costs for patients but not the healthcare system. This outcome was driven by a reduction in outpatient clinic visits. The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE) study found a statistically significant reduction in healthcare-associated costs for both patients and the healthcare system itself.10
Reduction in clinic presentation
Four studies, representing 1748 patients, reported data regarding the number of clinical reviews.10 11 13 17 One study documented no difference between the active and control arms.11 Three studies10 13 17 documented a statistically significant reduction in healthcare interactions in patients on RM compared with standard care which was driven by reduction of protocol defined follow-up and urgent in-office visits.
Discussion
This systematic review and meta-analysis of the effects of remote CIED monitoring were conducted in adults with HF with reduced ejection fraction and demonstrated that remote CIED monitoring did not reduce HF mortality or readmissions.
The overall benefit from RM is not in dispute.5 There is robust evidence that healthcare use overall is reduced,16 19 and there is more timely diagnosis of device complications and significant arryhthmias.17 20 However, there is no consistent evidence that hospital admissions are reduced—an especially important metric in patients with HF where frequent readmissions result in major morbidity. To date, the EVOLVO study is the only RM study that has documented a reduction in HF admissions, but this was a pooled outcome driven by a decrease in protocol-defined clinic visits and urgent in-office visits.
The reasons why a more prompt assessment of cardiac arrhythmia, device function and device-derived measures of well-being do not reduce HF readmissions remain unclear. One possible explanation arose in the Telemedical Interventional Management in HF II (TIM-HF2) trial. This trial was not included in this systematic review as not all patients had CIEDs but is important to discuss in this context.21 It included 30% of patients who had an ICD and 16% of patients who had CRT and demonstrated both had a small reduction in hospitalisation days for HF and all-cause mortality in patients with HF with RM. This study included clinical and patient measures including weight, blood pressure, heart rhythm, oxygen saturation and self-rated health status. The TIM-HF2 study suggests that a comprehensive implementation of RM, involving a combination of device and other measures, and collaboration between arrhythmia and HF physicians, might be a more effective strategy in the HF population than a simple device-based approach.
The trials of RM in HF have major limitations. All CIED types were not represented despite their widespread use. No studies included patients with single-chamber or dual-chamber pacemakers, despite evidence that up to 30% of such patients will have systolic HF and have not met the criteria for CRT or ICD therapy.22 No studies included patients with heart failure with preserved ejection fraction (HFpEF) even though up to 10% of the HFpEF population have a CIED.23 No studies included subcutaneous, leadless or conductive system pacing.
Implementation of RM also varied widely across the trials. For example, the IN-TIME study, the only study to document a decrease in mortality, required daily, implant-based, multiparameter central telemonitoring by trained staff before dissemination to local investigational sites.12 This form of RM, combined with telehealth, is more comprehensive than the methodology of other studies included in this analysis, some of which instituted RM without centralised training, oversight or with protocol-defined intervention.
A pooled analysis of the individual patient data from three trials (Lumos-T Safely RedUceS RouTine Office Device Follow-Up (TRUST), ECOST and Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME)), using the same home monitoring technology, demonstrated a statistically significant reduction in all-cause mortality and the composite endpoint of all-cause mortality or worsening HF hospitalisation.24 The results are encouraging but have to be interpreted with caution, as this was a post hoc and pooled analysis.
CIEDs and rapid use of RM technology, as is clear from our systematic review, lacks standardisation across CIED types, healthcare systems and supporting clinical services. There is a paucity of research in this area and, as such, our findings remain hypothesis generating. As is currently implemented, RM does not reduce mortality or hospital readmission.
Trial enrolment is often associated with positive outcomes in clinical research, often thought due to increased monitoring compared with standard care. Similarly, we postulate that comprehensive RM when integrated with telehealth programmes, as was employed by the IN-TIME investigators, which includes patient clinical data alongside device data, can improve patient mortality, but larger trials are required to confirm the magnitude, consistency and costs.
Conclusion
RM for patients with HF and CIEDs does not confer a demonstrable advantage with respect to HF outcomes. As currently implemented, RM does not provide a benefit with respect to all-cause mortality, HF readmissions or decreased therapy from ICDs. There was a trend towards reduced patient healthcare expenditure driven predominantly by reduced clinic presentations. Further well-designed, adequately powered, randomised controlled studies are required to determine the effectiveness of RM of CIEDs in patients with HF.
Data availability statement
Data are available upon reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
References
Supplementary materials
Supplementary Data
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Footnotes
Twitter @SverdlovAaron
Contributors All authors played a role in the design, drafting, revision and review of the manuscript and read and approved the manuscript. MM, SB and MR: methodology, data curation, writing—original draft and supervision. AS, MM, AB, SS, MR and SS: conceptualisation, methodology, writing—original draft and supervision. MM, NJ, SS, AB and JL: methodology, writing—original draft, validation editing and supervision. MM, MR, SB and SS: validation and formal analysis. AS is the guarantor for this work.
Funding This work is supported in part by the Entrepreneurs' Programme Innovation Connections Grants (from Entrepreneurs' Programme/Biotronik Australia Pty, App ID ICG000750 and ICG001079; AS and AB); Heart Foundation of Australia Future Leader Fellowship (award ID 101918, AS); 2018 NSW CVRN Ministerial Award for Rising Stars in Cardiovascular Research (AS); and RACP/Foundation for High Blood Pressure Research Establishment Award (AS).
Competing interests AS received speaker fees/honoraria from Novartis Australia, Bayer Australia and AstraZeneca Australia; research and educational grants from Bristol-Myers Squibb Australia Pty, Cellgene Pty, Biotronik Australia, Vifor Pharma and Roche Diagnostics.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.