Introduction
Approximately 500,000 patients worldwide are diagnosed with advanced heart failure (AHF), which means they are symptomatic and are not responding well to standard medical treatment.1 Heart failure (HF) is a progressive disease that can significantly affect quality of life. Over five million residents of the United States and nearly 15 million people worldwide have HF.2 People affected by HF experience physical activity limitations, have higher mortality rates and have overall diminished quality of life.3 Because HF is not a curable disease and can have considerable disabling effects on daily living, health-related quality of life is also negatively affected.4 There can be many causes of HF, including damage from myocardial infarction, coronary artery disease, myopathies, uncontrolled high blood pressure, congenital heart disabilities, lethal dysrhythmias or valve disease.5 The American Heart Association has described narrative stages of HF using the New York Heart Association (NYHA) functional classification (Table 1).5,6
The functional classes range from class I, in which patients have no limitations on physical activity and are symptom-free, to class IV, in which patients are severely symptomatic and unable to perform physical activities or activities of daily living.5 Advanced heart failure may be defined as NYHA functional classification III-IV, an ejection fraction of 20-30%, decreased systolic function, or very little to no symptom relief with standard medical treatment.7 The inability to perform routine care, cooking, or shopping, along with reduced exercise capacity and dependence upon others, puts this population at risk for decreased quality of life.8 As an end result, quality-of-life measures decrease.9
Advances in health care are credited with people living longer, but with longevity, the prevalence of HF diagnoses are increasing.1 Treatment goals include symptom management, optimizing medication and dietary compliance.7 Improving functional classes and relieving symptoms are associated with better health-related quality of life.4 Standard medical treatment for AHF includes, but is not limited to: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, diuretics, use of inotropes and cardiac resynchronization therapy.7 As HF worsens, patients experience frequent hospitalizations for exacerbations, hypotension in the presence of inotropic support, and organ damage from insufficient blood flow and pressure.7 The one-year survival rate once a patient has been diagnosed with AHF is as low as 6%.1 The preferred treatment for patients who remain symptomatic after standard medical treatment is heart transplantation.1 However, the shortage of donor organs and the difficulty in donor matching makes transplantation unlikely for thousands in need.5,7 Worldwide, approximately 2200 hearts are available for donation yearly, which does not meet the demand.1
In the United States, use of left ventricular assist devices (LVAD) was approved by the Food and Drug Administration as a bridge to transplant for patients with AHF in 1994. The initial goal was for short-term use until a donor's heart was available and suitable for transplant.10 Implantation of LVADs increased after the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH)10,11 trial reported that patients who were ineligible for heart transplantation and were implanted with an LVAD for destination therapy had increased survival rates compared to standard medical treatment.11 Destination therapy is ideal for patients who are not suitable for transplant, hemodynamically unstable and not responding to medical management.2 In the United States from 2006 to 2012, LVADs for destination therapy increased from six to more than 600 yearly.12 Currently, in the United States and Europe, more than 2500 and 2000 LVADs, respectively, are implanted annually.7 Left ventricular assist devices are not without significant risks and complications.13 Adverse events include bleeding, infections, stroke, right ventricular failure, abnormal heart rhythms, renal and hepatic dysfunction, thrombus and pump failure requiring replacements.1,13
Abshire et al.14 synthesized evidence evaluating the functional status of AHF patients with a recently implanted LVAD. Although quality of life was not a primary outcome of this study, there were significant functional gains throughout the first six months to one year. Results showed a NYHA functional improvement from class III-IV to class I-II and improvement in physical activity.14 This systematic review included six studies that evaluated improvement in functional status and only one study that reported quality-of-life findings among patients <70 and >70 who had an LVAD. Synthesis suggests there is no significant difference in the quality of life over time among this population. The type of device therapy was not indicated (bridge to transplant or destination therapy), and no quality-of-life scores were represented. There were recommendations for further studies that focus on better patient selection to improve outcomes and maximize functional ability and quality of life.14
Newt et al.15 conducted a systematic review that compared patients with a continuous flow LVAD to patients treated with standard medical treatment and found higher survival rates in the continuous flow LVAD groups. Quality of life was reported at one year using the Minnesota Living with Heart Failure Questionnaire, and LVAD patients reported improved quality of life over patients managed with standard medical treatment.15 This systematic review suggests survival gains from the LVAD placement over standard medical treatment can range from six months to almost two years.15 Brouwers et al.16 conducted a systematic review that compared LVAD patient-reported outcomes on health status and quality of life to recipients of heart transplants. Improved self-reported quality of life with the use of the LVAD from baseline scoring was reported, but the quality of life of those with an LVAD was not superior to heart transplantation.16 All of the studies represented in the systematic review found significant improvement in the mean health status score at follow-up compared to baseline date but plateaued at approximately three months. This score was represented by the Minnesota Living with Heart Failure Questionnaire.16
An umbrella review is needed to evaluate the best available evidence from research syntheses, as findings determining quality of life in AHF patients with an implanted LVAD vary substantially.8 The long-term prognosis and quality of life are limited in patients with AHF.2 Patients may exhibit HF symptoms an average of 6.65 years and may report psychological effects of depression, anxiety and withdrawal from socializing.17,18 Consolidating the best available evidence from research synthesis regarding quality of life, survival rates and changes in functional classification informs the clinician, patient and family so they may better collaborate in planning care. With the availability of survival statistics, concise information regarding functional improvements and health-related quality of life data, the clinician can provide patients and families with a quick overview of the similarities and differences among standard medical treatment, implanted LVADs and heart transplantation. Subsequently, this may promote more timely and appropriate treatment plan decisions. Significant adverse effects are associated with LVAD management, requiring a lifelong commitment from both patient and caregivers. Thorough educational briefing about common and known adverse events adds to the information that patients and family members need when considering the additional risk entailed with LVAD placement. Furthermore, the average life expectancy after LVAD placement is a factor when considering all treatment modalities.7
A preliminary search for systematic reviews and meta-analyses on the topic was conducted in April and November 2018 using PubMed, Embase, Cochrane Database of Systematic Reviews, Scopus, PROSPERO, Campbell Collaboration, and JBI Database of Systematic Reviews and Implementation Reports. The search revealed no umbrella reviews (either published or in progress) on the topic. The objective of this review is to evaluate the effectiveness of an implanted LVAD versus standard medical care or heart transplantation on quality of life in patients with AHF.
Review question
What is the effectiveness of an implanted LVAD compared to standard medical care or heart transplantation on quality of life in patients with AHF?
Inclusion criteria
Participants
This umbrella review will consider research syntheses that include patients who are 16 years of age or over with AHF. Patients may have an implanted device for bridge to transplant or destination therapy. Studies will include patients diagnosed with AHF based on one or more of the following criteria: NYHA functional classification III-IV, an ejection fraction of 20-30%, decreased systolic function, or little to no symptom relief with standard medical treatment.6 Included patients may be representatives of any hospital setting (rural or urban) and have additional comorbidities. Studies that include participants who are under 16 years of age, HF patients without a LVAD device, and HF patients who are not in advanced failure will be excluded from this umbrella review.
Intervention(s)
This umbrella review will consider research syntheses that evaluate patients who have implanted LVADs due to AHF. The patients may have first-, second-, or third-generation devices, and devices will include those placed for bridge to transplant or destination therapy roles. Bridge to transplant is a temporary solution for AHF patients who are hemodynamically unstable with no qualifying donor candidates. Destination therapy is ideal for patients who are not suitable for transplant, are hemodynamically unstable, and are on optimized medical regimens. This therapy is intended to be permanent.2
Comparator(s)
This review will compare the intervention to AHF patients treated with standard medical treatment or heart transplantation.
Outcomes
The primary outcome of this umbrella review is quality of life. Quality of life will be measured by tools and self-reports up to 24 months after treatment for AHF. These tools and self-reports may include, but are not limited to, the Minnesota Living with Heart Failure Questionnaire and Kansas City Cardiomyopathy Questionnaire.16 Beneficial and adverse outcomes will be addressed. Beneficial outcomes include greater ability to perform care more independently, which can be measured by self-reporting of improvement and a reduction in NYHA classification (from class IV to class II). Adverse outcomes include mortality.
Secondary outcomes include patient survival rates measured by reported mortality rates after treatment for AHF and the NYHA functional classification changes (before and after treatment for AHF).
Types of studies
This umbrella review will consider quantitative systematic reviews, meta-analyses and other reviews of empirical research studies. The types of studies included in an umbrella review are exclusively syntheses of existing research from systematic reviews (using internationally accepted methodologies) and meta-analyses. Studies published in English will be included. Studies published from 1994 to present will be included. In the United States, use of LVADs was approved by the Food and Drug Administration as a bridge to transplant for patients with AHF in 1994.10
Methods
The proposed systematic review will be conducted in accordance with JBI methodology for umbrella reviews.19
Search strategy
The search strategy will aim to find both published and unpublished studies. An initial limited search of PubMed and CINAHL has been undertaken to identify articles on this topic, followed by analysis of the text words contained in the titles and abstracts, and of the index terms used to describe these articles. This informed the development of a search strategy including identified keywords and index terms, which will be tailored for each information source including key terms "systematic" and "meta-analysis." A proposed search strategy for PubMed is detailed in Appendix I. The reference list of all studies selected for critical appraisal will be screened for additional studies.
Information sources
The databases/sources to be searched include: PubMed, CINAHL, Embase, Cochrane Database of Systematic Reviews, Scopus, PROSPERO, Campbell Collaboration, JBI Database of Systematic Reviews and Implementation Reports and Europe PubMed Central.
The search for unpublished research syntheses will include: MedNar, ProQuest Dissertations and Theses Database Science and Engineering Collection, OpenGrey, CORE and PapersFirst.
Study selection
Following the search, all identified citations will be collated and uploaded into EndNote (Clarivate Analytics, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Research syntheses that may meet the inclusion criteria will be retrieved in full and their details imported into JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI; JBI, Adelaide, Australia). The full text of selected citations will be retrieved and assessed in detail against the inclusion criteria by two independent reviewers. Full-text research syntheses that do not meet the inclusion criteria will be excluded, and reasons for exclusion will be provided in an appendix in the final systematic review report. Included studies will undergo a process of critical appraisal. The results of the search will be reported in full in the final report and presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.20 Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.
Assessment of methodological quality
Retrieved research syntheses that meet inclusion criteria will be critically appraised by two independent reviewers for methodological quality in the review using the standardized JBI critical appraisal instrument for systematic reviews and research syntheses.19 All reviews will be considered regardless of methodological quality since these reviews are few in number. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer. The results of critical appraisal will be reported in a narrative form and a table.
Data extraction
Data will be extracted from research syntheses included in the umbrella review using the standardized JBI data extraction tool for systematic reviews and research syntheses by two independent reviewers.19 The data extracted will include specific details about the objectives, type of review, participants, setting, the scope of database searching, dates of the search, date range of included research syntheses, number of included research syntheses, details of critical appraisal and quality assessment, the method of synthesis/analysis and outcomes. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer. Authors of syntheses will be contacted to request missing or additional data, where required.
Data summary
The aim of this umbrella review is to present a summary of existing research syntheses. The results of all included studies will be presented in an interpretable overview of the findings. Tabular presentation of the findings will be produced when overall effect estimates extracted from systematic reviews or other similar numerical data are presented. If quantitative data is presented, the number of studies that inform the outcome, the participants (from the included study) and the heterogeneity of the results of the included study will also be reported. A final Summary of Evidence will be presented to provide a simple visual indication of the findings of the review.
Assessing certainty in the findings
A Summary of Findings will be created using GRADEpro (McMaster University, ON, Canada). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the quality of evidence will be followed. The Summary of Findings will present the following information where appropriate: absolute risks of treatment and control, estimates of relative risk, and a ranking of the quality of evidence based on study limitations (risk of bias), directness, heterogeneity, precision and risk of publication bias of the review results.
Acknowledgments
This work contributes toward a Doctor of Nursing Practice for DA.
Appendix I: Search strategy for PubMed
1. "Heart Failure"[Mesh] or "AHF" or "ESCHF" or "HF" or "advanced heart failure" or "end stage congestive heart failure" or "heart failure"
2. "Quality of Life"[Mesh] or "quality of life"
3. "Heart-Assist Devices"[Mesh] or "Left Ventricular Assist Device" or "LVAD" or "heart assist device" or "continuous flow assist device'
4. "Systematic Review" or "meta analysis" or "meta analyses"
5. #1 AND #2 AND #3 AND #4
Limit to English from 1994
References