Author + information
- Received December 1, 2017
- Revision received March 28, 2018
- Accepted March 28, 2018
- Published online August 27, 2018.
- Tiana Nizamic, MDa,
- M. Hassan Murad, MDb,
- Larry A. Allen, MD, MHSc,
- Colleen K. McIlvennan, DNP, ANPc,
- Sara E. Wordingham, MDd,
- Daniel D. Matlock, MD, MPHe and
- Shannon M. Dunlay, MD, MSf,∗ ()
- aDepartment of Medicine, University of Colorado at Denver, Denver, Colorado
- bDivision of Preventive, Occupational, and Aerospace Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota
- cDivision of Cardiology, Department of Medicine, University of Colorado, Denver, Colorado
- dSection of Palliative Medicine, Department of Medicine, Mayo Clinic, Scottsdale, Arizona
- eDivision of Geriatrics, Department of Medicine, University of Colorado at Denver, Denver, Colorado
- fDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
- ↵∗Address for correspondence:
Dr. Shannon M. Dunlay, Mayo Clinic, 200 First Street South West, Rochester, Minnesota 55905.
Objectives This study sought to systematically review the available evidence of risks and benefits of ambulatory intravenous inotrope therapy in advanced heart failure (HF).
Background Ambulatory inotrope infusions are sometimes offered to patients with advanced Stage D HF; however, an understanding of the relative risks and benefits is lacking.
Methods On August 7, 2016, we searched SCOPUS, Web of Science, Ovid EMBASE, and Ovid MEDLINE for studies of long-term use of intravenous inotropes in outpatients with advanced HF. Meta-analysis was performed using random effects models.
Results A total of 66 studies (13 randomized controlled trials and 53 observational studies) met inclusion criteria. Most studies were small and at high risk for bias. Pooled rates of death (41 studies), all-cause hospitalization (15 studies), central line infection (13 studies), and implantable cardioverter-defibrillator shocks (3 studies) of inotropes were 4.2, 22.2, 3.6, and 2.4 per 100 person-months follow-up, respectively. Improvement in New York Heart Association (NYHA) functional class was greater in patients taking inotropes than in controls (mean difference of 0.60 NYHA functional classes; 95% confidence interval [CI]: 0.22 to 0.98; p = 0.001; 5 trials). There was no significant difference in mortality risk in those taking inotropes compared with controls (pooled risk ratio: 0.68; 95% CI: 0.40 to 1.17; p = 0.16; 9 trials). Data were too limited to pool for other outcomes or to stratify by indication (i.e., bridge-to-transplant or palliative).
Conclusions High-quality evidence for the risks and benefits of ambulatory inotrope infusions in advanced HF is limited, particularly when used for palliation. Available data suggest that inotrope therapy improves NYHA functional class and does not impact survival.
An estimated 6.5 million adult Americans are living with heart failure (HF), and the prevalence is expected to increase. A fraction of those patients have advanced (Stage D) HF characterized by symptoms that limit daily life and are refractory to usual recommended therapies (1). Patients with advanced HF are sometimes offered ambulatory intravenous inotropic support, either while awaiting cardiac transplantation (a Class IIa recommendation) (1) or as an advanced palliative therapy (a Class IIb recommendation) (1). Use of ambulatory inotropes increased markedly from 2010 to 2014 among Medicare beneficiaries (2). However, in 2013 American College of Cardiology Foundation/American Heart Association HF guidelines, both recommendations were acknowledged to be based upon limited evidence (Level of Evidence: B) (1).
An understanding of the risks and benefits associated with use of inotropes on an outpatient basis is vital to the patient’s ability to make an informed decision, the clinician’s confidence in making a recommendation, and the payer’s willingness to cover the costs of their use. Although inotrope therapy was initially touted as an exciting alternative that would restore normal cardiac hemodynamics and alleviate symptoms (3), concerns were raised when studies demonstrated a higher incidence of ventricular arrhythmia and sudden death with inotropes (4,5). Contemporary comprehensive reviews of relative risks and benefits of chronic ambulatory inotrope infusions are lacking. Within this setting, use of intravenous inotropes is variable across clinicians, centers, and regions (6).
To address these gaps in knowledge, we sought to systematically review the available evidence of the risks and benefits of ambulatory intravenous inotropes in patients with advanced HF.
This systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
On August 7, 2016, we searched SCOPUS, Web of Science, Ovid EMBASE, and Ovid MEDLINE for articles containing the terms “inotrope,” “heart failure”; synonyms of “advanced” (end-stage, Stage D, refractory, class IV, terminal), “palliative” (home, end of life, hospice), and “heart transplantation.” The full search strategy is described in Online Appendix. We also manually scanned reference lists to identify additional articles.
Eligibility criteria and study selection
We included randomized controlled trials (RCTs), observational studies, and case series of adult human subjects with advanced HF. We included studies published in all years. We required studies to have at least 1 arm that included participants treated with long-term intravenous inotrope infusions (milrinone, dobutamine, dopamine, or levosimendan) as outpatients. Long-term use was defined as either indefinite (palliative) therapy or as bridge-to-heart transplantation (BTT). If inotrope administration was part of a study protocol, the intended treatment duration had to be at least 4 weeks. Inotrope infusions could be administered either continuously or intermittently. We included studies in which intermittent inotropes were administered in a monitored setting (such as a clinic) if patients were outpatient between infusions. We excluded studies of inotropes in patients hospitalized with acute decompensated HF. We restricted studies that reported primary data for at least 1 of our outcomes of interest. We excluded single case reports, non-English language articles, reviews, editorials, meeting abstracts, and studies of oral inotropes. Two study team members (T.N., S.M.D.) independently reviewed all titles and abstracts identified by the search strategy. Abstracts that potentially met study criteria were identified, and the full-text articles were reviewed in duplicate to determine the final included studies.
Outcomes included death, where death occurred, hospitalization (all-cause and HF-related), health-related quality of life (HRQOL), functional status (New York Heart Association [NYHA] functional class, 6-min walk test [6MWT] distance), ventricular arrhythmias (sudden death, sustained ventricular arrhythmias, nonsustained ventricular tachycardia [NSVT], implantable cardioverter-defibrillator [ICD] shocks), central line complications (infection, deep venous thrombosis), cost, and hospice enrollment. We were intentionally broad in inclusion of outcomes to capture all studies that provide relevant insight to stakeholders. Study data were abstracted (T.N.) and manually verified (S.M.D.). In ancillary analyses, we examined reported changes in cardiac structure/function and hemodynamics on inotropes among included studies.
Risk of bias assessment
The risk of bias was assessed for studies with a non-inotrope control group. We used the Cochrane risk-of-bias tool for randomized trials (Online Ref. 1) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool in nonrandomized studies of interventions (Online Ref. 2). These domain-based assessments consider different types of bias in studies that are important in interpreting results (see the Online Appendix for additional details).
For binary outcomes, event rates are reported as the number of events per 100 person-months follow-up with 95% confidence intervals (CIs) derived from the Poisson distribution. Meta-analysis of event rates was performed by using the random effects model as described by DerSimonian and Laird (7). The risk of death in patients treated with inotropes compared with that in controls in RCTs was pooled using a random effects model, with results presented as risk ratio (RR) with 95% CI. For continuous outcomes, random effects models were used to compare, first, differences in NYHA functional class while taking inotropes compared with baseline, and, second, differences in NYHA functional class in patients treated with inotropes compared with controls in RCTs. Results are presented as mean differences and 95% CI. Mortality and NYHA functional class were the only outcomes with sufficient RCT data to enable pooled comparisons of patients treated with inotropes and controls. We used the I2 statistic to assess heterogeneity (8). Stratified analyses were performed as follows to explore heterogeneity by: 1) inotrope indication (palliative vs. BTT); 2) method of inotrope delivery (intermittent vs. continuous); and 3) study design (RCT vs. observational). Analysis was performed using Stata version 13.0 software (College Station, Texas) and Review Manager version 5.3 software (RevMan 5.3, Nordic Cochrane Center, Copenhagen, Denmark).
The search strategy identified 955 abstracts, of which 63 met inclusion criteria. An additional 3 articles were identified by reviewing reference lists. This strategy resulted in 66 articles, including 13 RCTs, 4 nonrandomized controlled trials, and 49 observational studies (Figure 1, Table 1, Online Tables 1 and 2). Most studies were small (median of 34.5; range 2 to 471 patients per study). The most common inotrope used was dobutamine (74.2% of studies). Inotropes were more often administered intermittently than continuously (50.0% vs. 31.8%, respectively).
Risk of bias
Of 13 RCTs, only 1 trial was at low risk for bias, 3 had unclear risk, and 9 had high risk for bias (Online Table 3). Of 15 studies that compared patients taking inotropes to a control population, most cases were at critical (7 studies) or at serious (6 studies) risk of bias (Online Table 4).
A total of 58 studies reported occurrences of death in patients treated with inotropes; the rate of death per month of follow-up could be calculated for 41 studies (Online Figure 1). The rate of death ranged from 0 to 44.4 with a pooled rate of 4.2 (95% CI: 3.2 to 5.5) deaths per 100 person-months receiving inotrope therapy. Rates of death were not statistically different in studies of inotropes as palliative therapy (10.5 per 100 person-months; 95% CI: 4.8 to 22.8; 4 studies) compared with BTT (5.0 per 100 person-months; 95% CI: 2.7 to 9.1; 7 studies; p value for interaction = 0.41). Rates of death in studies administering inotropes continuously (4.2 per 100 person-months; 95% CI: 2.6 to 6.9; 14 studies) were similar to those studies in which inotropes were administered intermittently (3.3 per 100 person-months; 95% CI: 2.0 to 5.4; 22 studies; p = 0.75). Rates of death in trials (2.9 per 100 person-months; 95% CI: 1.4 to 6.1) were similar to those in observational studies (4.9 per 100 person-months; 95% CI: 3.7 to 6.6; p = 0.57).
Nine RCTs (including 434 patients) compared mortality in patients treated with inotropes to a non-inotrope control population (4 to placebo infusions [9–12], 2 to other infusions [13,14], and 3 to usual care [15–17]). Only 1 RCT reported a significantly lower risk of death in patients randomized to dobutamine plus amiodarone than in patients receiving placebo (11). In pooled analysis, there were no differences in mortality over a median 5.3 months of follow-up (RR inotrope vs. control: 0.68; 95% CI: 0.40 to 1.17; p = 0.16) (Figure 2). Results were similar in placebo-controlled studies (RR: 0.56; 95% CI: 0.25 to 1.24; p = 0.15). A funnel plot revealed no asymmetry to suggest publication bias (Online Figure 2).
Location of death
Five observational studies reported locations of death in patients treated with inotropes: 2 studies used inotropes as palliative therapy (18,19), 2 as BTT (20,21), and 1 included patients with both indications (22). The proportion of deaths at home versus in the hospital ranged from 7.1% (22) to 64.5% (19), respectively, with the highest proportions occurring in the studies of inotropes as palliative therapy (18,19).
In 15 studies, the rate of all-cause hospitalization per 100 person-months of follow-up ranged from 9.7 to 55.1, with a pooled rate of 22.2 (95% CI: 18.0 to 27.4) (Figure 3). Similarly, in 15 studies, the rate of HF hospitalizations ranged from 0 to 41.7, with a pooled rate of 10.1 HF hospitalizations per 100 person-months (95% CI: 7.3 to 13.9) (Online Figure 3). There were no differences in rates of all-cause or HF hospitalizations by delivery method, by indication, or by study design (p value for interactions >0.10).
There were insufficient data to compare the risk of hospitalizations in patients treated with inotropes versus controls. Eleven studies compared hospitalizations before and after inotrope initiation in the same population (21–24, Online Refs. 23,33–35,39,44,68). Although all 11 studies reported a decline in hospitalizations or days hospitalized while taking inotropes, most studies did not account for differential follow-up due to death during inotrope therapy. A single study of Medicare beneficiary outpatients receiving inotropes accounted for follow-up and observed a decline in average number of days hospitalized per beneficiary, from 13.3 in the month prior to beginning inotropes to 4.4, 4.0, and 2.3 days per month in 30, 60, and 180 days, respectively, after inotrope initiation (24).
Only 3 studies of intermittent inotrope therapy including 99 patients compared all-cause hospitalizations with inotropes with a non-inotrope control population (10,17,25). Repasos et al. (25) reported a higher rate of 6-month hospitalization in patients treated with inotropes versus renal replacement therapy (mean: 1.9 vs. 0.5 per person, respectively; p = 0.001) (25). Elis et al. (10) found no differences in 6-month HF hospitalizations in 19 patients randomized to dobutamine versus placebo (mean: 2.2 vs. 2.1 per person, respectively; p = 0.11). The final study reported 11 total hospitalizations in 6 months in patients taking dobutamine compared with 17 in controls (17).
Functional status and quality of life
In total, 30 studies presented NYHA functional class before and during use of inotropes, of which 24 included sufficient information to pool data. Of 485 unique patients with NYHA functional class assessed pre-inotropes, 424 (87%) survived to have NYHA functional class reassessed. Prior to inotropes, all patients were NYHA functional class III or IV. Participants experienced a mean improvement in NYHA class of 1.2 (95% CI: 1.0 to 1.4; p < 0.001) (Figure 4A) taking inotropes. Although all studies demonstrated an improvement in NYHA functional class taking inotropes, heterogeneity was high (I2 = 89%). NYHA functional class improved in studies (23,26,27) that treated patients with inotropes as palliative therapy (mean: −1.1 class; 95% CI: 0.8 to 1.3; I2 = 0%) and as BTT (mean: −1.3 classes; 95% CI: 1.2 to 1.4; I2 = 0%) (21,28,29).
Just 5 RCTs compared NYHA functional class while taking intermittent inotropes to a control population (2 studies vs. placebo infusions) (11,12), 1 versus prostaglandin E1 infusion (13), 1 versus furosemide infusion (30), and 1 versus usual care (15). Participants treated with intermittent inotrope infusions had lower NYHA functional class (mean difference: 0.6 class; 95% CI: 0.2 to 1.0; p = 0.001) (Figure 4B).
Only 4 studies reported 6MWT distances in patients taking inotropes (Online Table 5). Two of three studies (9, Online Refs. 12,36) that compared 6MWT distance taking inotropes with baseline reported an improvement taking inotropes. Two studies measured 6MWT distances in patients treated with inotropes versus those receiving placebo. In 1 study (9), 6MWT distances improved in patients treated with both levosimendan and placebo, and the difference was not significant. The other study reported a 23% improvement taking inotropes compared to a 1% decline in subjects taking placebo (p < 0.001) (31).
Six studies reported results of health-related quality of life (HRQOL) assessments in patients treated with inotropes (Online Table 6). All 4 studies that compared HRQOL before and after inotrope initiation reported improvement with inotropes (9,31,32, Online Ref. 12). However, the 2 studies that compared improvement in HRQOL in patients treated with inotropes versus placebo found no differences (9,31).
A total of 41 studies reported the frequency of ventricular arrhythmia or sudden death in patients taking inotropes (Online Table 7). Many studies were published prior to widespread use of ICDs, and capture of ventricular arrhythmias using other methods varied. In 4 contemporary reports of continuous inotrope infusions (21,32–34), the incidence of ICD shocks was similar, ranging from 2.2 to 3.0 per 100 person-months of follow-up, with a pooled incidence of 2.4 (95% CI: 2.1 to 2.8), whereas 20 studies reported sudden death events were rare (0 to 6 events per study), and given the variability in ICD use across studies, results were not pooled. Eight studies compared ventricular arrhythmias in patients treated with inotropes versus those in controls. Mavrogeni et al. (16) found no differences in the mean number of NSVT episodes captured using a Holter monitor in individuals treated with intermittent levosimendan versus controls (12 vs. 13, respectively; p = 0.19). Event rates were otherwise too small to draw meaningful conclusions.
Few studies provided insight as to whether amiodarone abrogates the arrhythmogenicity of inotropes. Nanas et al. (35) first compared 11 consecutive patients treated with intermittent dobutamine infusions (as needed) without amiodarone to 11 subsequent patients treated with weekly dobutamine plus amiodarone, 400 mg/day. One-year survival in those receiving amiodarone was 55% compared with 9% in those not taking amiodarone (p = 0.011). These same investigators later randomized 30 patients to intermittent dobutamine or placebo infusions; all patients received amiodarone, 400 to 800 mg/day (11). The authors reported higher 1-year (69% vs. 28%; p = 0.019) and 2-year (44% vs. 21%; p = 0.041) survival rates in patients receiving dobutamine, suggesting that intermittent dobutamine infusions may improve survival when accompanied by amiodarone. Finally, Tsagalou et al. (36) assessed ventricular ectopy by using 24-h electrocardiography recordings on the day prior to and on the days of intermittent dobutamine infusions in 30 patients taking amiodarone, 400 mg/day. There were no significant differences in mean ventricular ectopic beats in the total population, although dobutamine was pro-arrhythmic in 4 patients. These small studies suggest that amiodarone may provide some protection against potential pro-arrhythmic effects of intermittent dobutamine infusions.
Central line complications
A total of 26 studies reported the frequency of central line complications in patients treated with inotropes (Online Table 8). Among the 13 studies that provided enough information to pool data and exclude overlapping patient populations, the rate of central line infection varied from 0 to 9.8 per 100 person-months of follow-up, with a cumulative rate of 3.6 per 100 person-months (95% CI: 2.4 to 5.4). Haglund et al. (37) observed 9.8 infections per 100 person-months in 129 patients awaiting transplant at a single center. In 4 studies the incidence of catheter-related thrombosis ranged from 0 to 5.7 per 100 person-months follow-up (21,37, Online Refs. 7,41).
Nine studies compared the costs of outpatient inotrope infusion to those in a control population (Online Table 9). Five studies found an outpatient strategy to be cost saving compared with ongoing hospital-based care in patients awaiting heart transplantation (28,29,32, Online Refs. 13,66). The other 4 studies compared costs of inotropes to those of a pre-inotrope period in the same patients. The study by Hauptman et al. (24) was the only study to account for the costs of outpatient inotrope infusions and reported cost savings in patients who died within 180 days, attributable primarily to decreased hospitalizations. There were no studies comparing costs associated with outpatient inotropes versus hospice care in patients who were not candidates for heart transplantation.
Only 1 study reported the proportion of patients receiving inotropes who were enrolled in hospice (38). Of 19 decedents, only 7 were said to have “required” hospice or palliative care treatment prior to death, although it is unclear what criteria were used to determine who would benefit from these services.
A total of 17 studies reported hemodynamics at baseline and while taking inotropes (Online Table 10). Most studies reported patients’ cardiac indices were higher and that pulmonary capillary wedge pressures were lower during inotrope therapy. A total of 17 studies reported echocardiographic findings both pre-inotrope and after initiation of inotropes (Online Table 11). Several studies reported significant improvements in ejection fraction and left ventricular size on inotropes compared with baseline.
There were several important findings from this systematic review. First, the quality of data assessing the risks and benefits of ambulatory intravenous inotropes, even among RCTs, is limited, which warrants careful consideration when interpreting results. Second, most studies were small, and thus, estimates are plagued by wide confidence intervals. Third, data for inotropes as palliative therapy are particularly lacking, which limited our ability to summarize comparative risks and benefits in most patients with advanced HF who are not eligible for mechanical circulatory support or transplantation. However, based upon available evidence, inotrope infusions appear to improve NYHA functional class. Limited evidence suggests inotropes do not increase the risk of death. Although hospitalizations and ventricular arrhythmias are common, there is insufficient evidence to conclude whether inotropes affect the risk of these events. Finally, outpatient inotrope infusions are relatively expensive, and although they appear to be cost-saving compared with ongoing hospitalization in a BTT population, it is unclear whether they are cost-effective as palliative therapy.
Most studies of outpatient inotrope infusions were observational, and many reported the experience of patients treated with inotropes without a comparison group. Even among studies with a comparison group, the most common design used was pre/post. This becomes problematic for outcomes such as HRQOL, which tends to improve following HF hospitalization regardless of therapy. The influence of death on other outcomes, such as hospitalization, was inadequately accounted for in many studies where the number of survivors on inotropes dwindled over time but was overlooked as a potential reason why fewer hospitalizations occurred. The assessment of nonfatal outcomes such as hospitalizations, NYHA functional class, and HRQOL can be problematic in a population with such a high rate of death. The sickest individuals are not represented in follow-up and can contribute to survivor bias.
The only outcome in which there was consistent evidence favoring inotropes was improvement in NYHA functional class. However, although 5 RCTs compared NYHA functional class while taking inotropes to a control population (11–13,15,30), all of them administered inotropes as intermittent infusions. Similarly, 9 RCTs compared risks of death while receiving inotropes to a control population but only 1 administered inotropes as continuous infusions, and it only included BTT patients (14). The overall paucity of data for patients receiving continuous infusions and in those using inotropes as palliative therapy leave us to extrapolate observed results to these populations commonly encountered in contemporary practice. Furthermore, response to inotropes may differ by various patient factors, such as etiology of HF and ejection fraction. Studies are needed to identify patient phenotypes that may respond best to inotrope infusions.
Additionally, the indication for inotropes (palliation or BTT) is important in decision making. Mechanical circulatory support with a left ventricular assist device (LVAD) is used in more than one-half of patients awaiting transplantation, but for those who are not candidates for LVAD, inotropes may be the only strategy offered to maintain clinical stability and increase the likelihood of receiving a transplant. As such, BTT patients may weigh benefits and risks of alternative strategies differently than other patient populations.
Advanced HF clinicians who offer inotropes as palliation often explain their goal is to “improve symptoms but not survival.” Overall, our findings do not refute this notion, as NYHA functional class improved and there was no significant impact on mortality. As most studies were performed at a time when ICD use was rare; it is unclear if association of inotropes with risk of death would be more favorable with ICD use. However, the estimates lacked precision as studies were small. Most studies were not limited to patients receiving inotropes as palliation, which impairs our ability to apply these data to that population. Furthermore, patients considering inotropes as palliation have important options to consider including ongoing medical therapy with or without enrollment in hospice. There are no data comparing the risks and benefits of palliative inotropes with hospice. While some hospice agencies will consider enrolling patients on palliative inotropes (39), the cost of inotropes is often prohibitive due to the capitated, per diem reimbursement model of hospice (24,40). As such, inotropes can serve as a direct barrier to hospice enrollment. Furthermore, patient and clinician perceptions of inotropes may be clouded by advertisement from companies offering infusion therapy, which sometimes overstate the benefits of inotropes while rarely mentioning potential harm. Results of this review highlight the need for studies comparing the risks and benefits of palliative inotropes with alternative strategies in patients with advanced HF ineligible for LVAD or transplant.
We did not include studies of inotropes administered in patients hospitalized with acute decompensated HF. However, a recent trial of hospitalized patients found that levosimendan provided symptomatic relief but also increased the risk of hypotension and cardiac arrhythmias (41). Finally, although we excluded studies of oral inotropes as their use is not recommended (1), a large RCT found an increased risk of death and hospitalization in patients treated with outpatient oral milrinone (5).
We are forced to practice and make decisions using the data that we have. There are no large RCTs that delineate the risks and benefits of outpatient intravenous inotropes compared with those of alternative options. As such, a detailed review such as this provides information that can be tremendously helpful to clinicians, patients, and payers faced with making challenging decisions. Overall, available data suggest that patients treated with inotropes, on average, experience an improvement of one NYHA functional class regardless of indication (BTT or palliative). In addition, infection is a known complication of the need for a central line for inotrope delivery and available studies provide estimates of that risk. Finally, knowledge of the average observed rate of outcomes on inotropes may be beneficial in counseling patients considering inotropes on what to expect (Figure 5, Table 2). It is important to acknowledge that heterogeneity of pooled estimates was high for most outcomes, and users should view these rates as average across diverse settings.
Published studies fail to provide adequate information comparing the risks and benefits of ambulatory intravenous inotropes in populations encountered in contemporary clinical practice. The findings of this review should serve as a call for RCTs or well-designed observational studies of continuous inotrope infusions as palliation compared with other strategies.
COMPETENCY IN MEDICAL KNOWLEDGE: It is important for clinicians to understand the risks and benefits of outpatient inotropes when offering them to patients with advanced HF. Inotrope infusions improve NYHA functional class, but their impact on HRQOL and risks of hospitalization and ventricular arrhythmia are unclear.This review provides a summary of the available evidence on the risks and benefits of outpatient inotropes which can be used to more effectively counsel patients and families considering inotropes as a treatment option.
TRANSLATIONAL OUTLOOK: Additional research is needed to understand the risks and benefits of outpatient inotropes as palliation compared with those of other options.
Dr. Dunlay’s contribution was supported by U.S. National Institutes of Health grant K23 HL 116643. Dr. Allen has financial relationships with Boston Scientific, Cytokinetics, Novartis, Patient-Centered Outcomes Research Institute (PCORI), National Institutes of Health, and the American Heart Association. Dr. Matlock has received support from the American College of Cardiology Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- 6-min walk test
- bridge to transplant
- heart failure
- health-related quality of life
- implantable cardioverter-defibrillator
- nonsustained ventricular tachycardia
- New York Heart Association
- Received December 1, 2017.
- Revision received March 28, 2018.
- Accepted March 28, 2018.
- 2018 American College of Cardiology Foundation
- Yancy C.W.,
- Jessup M.,
- Bozkurt B.,
- et al.
- Gilstrap L.G.,
- DeFilippis E.M.,
- Stevenson L.W.
- Allen L.A.,
- Fonarow G.C.,
- Grau-Sepulveda M.V.,
- et al.
- Higgins J.P.,
- Thompson S.G.,
- Deeks J.J.,
- Altman D.G.
- Parissis J.T.,
- Adamopoulos S.,
- Farmakis D.,
- et al.
- Leier C.V.,
- Huss P.,
- Lewis R.P.,
- Unverferth D.V.
- Roig E.,
- Perez-Villa F.,
- Cuppoletti A.,
- et al.
- Repasos E.,
- Kaldara E.,
- Ntalianis A.,
- et al.
- Acharya D.,
- Sanam K.,
- Revilla-Martinez M.,
- et al.
- Hashim T.,
- Sanam K.,
- Revilla-Martinez M.,
- et al.
- Tsagalou E.P.,
- Gounopoulos P.,
- Terrovitis J.V.,
- et al.
- Haglund N.A.,
- Cox Z.L.,
- Lee J.T.,
- et al.
- Packer M.,
- Colucci W.,
- Fisher L.,
- et al.