The PALL-VAD Study: Palliative Care Intervention to Improve Health Related Quality of Life for Patients With Heart Failure on Long-Term LVAD Support: A Pilot, Prospective, Randomized Trial
The PALL-VAD Study: Palliative Care Intervention to Improve Health Related Quality of Life for Patients With Heart Failure on Long-Term LVAD Support: A Pilot, Prospective, Randomized Trial
Background: While left ventricular assist device (LVAD) therapy improves survival in patients with advanced heart failure (AHF), unique LVAD-related burdens may impact health-related quality of life (HRQoL). Palliative care specialists are key members of the multidisciplinary care team for patients with long-term-LVAD (LT-LVAD), offering specialized, comprehensive, holistic care.
Problem: A seminal study of palliative care in patients with heart failure (PAL-HF trial) demonstrated that outpatient palliative care improved HRQoL, depression, anxiety, and spiritual well-being compared to usual care. The impact of longitudinal palliative care on HRQoL in LT-LVAD patients is unknown.
Objective: The investigators aim to conduct the first study examining a palliative care intervention to improve HRQoL among LT- LVAD recipients (patients who have lived with LT-LVAD for at least six months and are not heart transplant candidates) at two centers (MedStar Health and Inova) in the Mid-Atlantic Region. Given the demographics of the study institutions, the investigators anticipate a socioeconomically and racially diverse cohort of patients with subgroups who may disproportionately experience LVAD-related burdens relative to benefits.
Aims: The first aim is to assess baseline measures of HRQoL in LT-LVAD patients to understand differences in HRQoL across subgroups and multiple, understudied domains. The second aim is to test the feasibility and acceptability of a randomized, unblinded pilot study of a palliative care interdisciplinary intervention in this population.
Significance: Results of this study will inform the development of a large randomized controlled trial to test the effectiveness of palliative care intervention in improving HRQoL in LT-LVAD patients. If results are positive, this will revolutionize the post-LVAD treatment paradigm, by making palliative care integration the standard of care for longitudinal LT-LVAD patient management.
SPECIFIC AIMS
Approximately 6 million adults in the United States carry a diagnosis of heart failure (HF) and the prevalence is expected to rise to 8 million by 2030. About 5% (300,000) HF patients per year develop end-stage or advanced heart failure (AHF). Mortality rates are high once a patient is diagnosed with AHF, with median survival of only one year. Only two therapies have demonstrated survival and quality of life benefit for AHF: heart transplantation (HT) and left ventricular assist device (LVAD). A significant proportion of patients with AHF are not eligible for HT, which remains a scarce resource with demand greatly outstripping donor supply. The advent of LVAD therapy has thus transformed the care of patients with AHF who cannot receive HT. Over 25,000 patients received LVADs in the period from 2010 to 2019. A majority of LVADs are implanted with intention of being long-term ("destination") therapy. Therefore, the number of patients living on long-term LVAD (LT-LVAD) therapy, (defined as patients not anticipated to be able to undergo HT due to nonmodifiable factors), continues to increase every year. As these patients experience age-related diseases such as cancer and dementia, their needs for symptom management and advance care planning will increase over time. Palliative care can play a major role in improving HRQoL for these patients.
Though patients with LVADs have improved survival compared to those medically managed, they experience unique LVAD-related harms that impact quality of life. Palliative care is a subspecialty with a crucial role in the care of HF patients, focused on improvement of quality of life and reduction of suffering in patients with serious illness throughout their disease trajectory. The Palliative Care in Heart Failure (PAL-HF) trial demonstrated that patients who received outpatient palliative care had consistent and significant improvements in HRQoL, depression, anxiety, and spiritual well-being scales compared to patients receiving usual care. However, no studies to date have examined the role or impact of palliative care in the LT-LVAD population.
Taken together, these studies highlight major gaps and opportunities to better understand factors associated with HRQoL in LT-LVAD patients and design interventions to improve their HRQoL. The investigators hypothesize that palliative care specialists can significantly improve HRQoL for all LT-LVAD patients, with the additional benefit of mitigating disparities in HRQoL among vulnerable populations.
The investigators seek to address these gaps and test these hypotheses in a study at two large AHF therapies centers in the mid-Atlantic region-MedStar Washington Hospital Center and Inova Schar Heart and Vascular Institute, which combined will enhance diversity, patient recruitment and study team expertise. The study team will consist of AHF and palliative care representation and leadership at both institutions to ensure success in studying the following aims:
Specific Aim 1: To establish baseline measures of HRQoL across multiple domains in a cross-section of 150 patients living with LT-LVAD and examine associations between adverse HRQoL and patient demographics, social determinants of health, and medical complications. The investigators hypothesize that women and historically marginalized populations with LT-LVAD are more likely to have lower baseline HRQoL.
Specific Aim 2: To implement an unblinded pilot study of 90 LT-LVAD patients randomized to a palliative care interdisciplinary intervention versus usual care and assess impact on HRQoL. The feasibility and acceptability of this intervention will be studied in this aim.
The goal of this study is to generate the data and knowledge needed to obtain an NIH R-series grant to fund a randomized controlled trial to test the efficacy of a structured, prospective palliative care intervention for LT-LVAD patients. If the results are positive, this will revolutionize the post-LVAD treatment paradigm, making integration of palliative care into longitudinal care of LT-LVAD patients the standard of care.
BACKGROUND AND SIGNIFICANCE Heart failure affects millions worldwide, with an estimated prevalence of 1-2% in the general population and up to 10% in those 70 years or older. In the United States, over 6 million adults have a diagnosis of HF, and the prevalence is rising. A subset (5% per year or approximately 300,000) will progress to AHF in whom mortality rates are high with median survival of only one year. Only two therapies have demonstrated a survival benefit for AHF: heart transplantation (HT) and left ventricular assist devices (LVAD). A significant proportion of patients with AHF are not eligible for HT, which remains a scarce resource with demand greatly outstripping supply.
LVAD therapy has transformed the care of patients with AHF who cannot receive HT. Over 25,000 patients received LVADs in the period from 2010 to 2019, and the number of patients living on LVAD therapy continues to increase every year. There are several indications for LVAD implantation-some are bridge to transplant, candidacy or to recovery, while in others it is long-term or lifelong therapy (LT-henceforth referred to as LT-LVAD) for patients who will not derive benefit from HT due to non-modifiable factors. In 2021, 81.1% of implanted LVADs were classified as LT therapy, compared to 50.4% of patients in 2014. These patients are at risk of age-related illnesses such as dementia and cancer, which can impose additional challenges to treatment, symptom-burden, and quality of life.
While LVAD therapy has improved survival in AHF, unique LVAD-related burdens still impact quality of life. Patients living with LVADs may suffer from a loss of autonomy due to debility from post-surgical deconditioning, loss of employment, increased reliance on caregivers and anxiety related to LVAD care and risk of mortality. The HRQoL of LT-LVAD patients remains inadequately described. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) for instance is the largest national registry of LVAD patients, however, it does not capture HRQoL beyond Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol 5-dimension (EQ-5D) scores leaving assessment of several important quality of life domains unstudied and undescribed, particularly in the LT-LVAD population.
Palliative care, a specialty that is focused on quality of life, may be well suited to improve HRQoL in LT-LVAD patients. Palliative care aims to improve quality of life and reduce suffering in patients with serious illness throughout their disease trajectory. A growing body of evidence increasingly highlights the crucial role of palliative care intervention in the heart failure population. The PAL-HF trial demonstrated that patients who received outpatient palliative care had consistent and significant improvements in HRQoL, depression, anxiety and spiritual distress scales compared to patients receiving usual care. However, no studies, to date, have examined the role or impact of palliative care in the LT-LVAD population.
Taken together, these studies underline major gaps in the understanding of factors associated with lower HRQoL in LT-LVAD patients and highlight opportunities to design interventions to improve HRQoL in all LT-LVAD recipients. Opportunities additionally exist to reduce disparities in HRQoL in women and marginalized populations, who are often overlooked in cardiovascular outcomes research yet disproportionately experience the burdens of LT-LVAD relative to the benefits. Our proposed research aims to fill these gaps. The investigators hypothesize that women and historically marginalized populations with LT-LVAD are more likely to have lower baseline HRQoL across multiple domains, and that palliative care intervention may significantly improve HRQoL for all LT-LVAD patients, with the additional benefit of mitigating disparities in HRQoL among subgroups.
The palliative care and AHF teams are closely intertwined at both MedStar Washington Hospital Center Heart and Vascular Institute (MHVI) and Inova Schar Heart and Vascular (ISHV). The spectrum of collaboration includes the clinical care of patients prior to and following LVAD implantation. Given growing evidence demonstrating the beneficial impact of palliative care on patients' quality of life, and the inconsistent involvement of palliative care in patients with LT-LVAD at the study institutions, the proposed research aims to first comprehensively quantify the burden of HRQoL across several understudied domains in a large LT-LVAD population at two centers in the Mid-Atlantic Region. Next, it aims to study the feasibility and acceptability of a randomized, unblinded palliative care intervention on HRQoL in LT-LVAD patients. Combining two large centers will enhance diversity, patient recruitment and study team expertise.
If this study demonstrates feasibility and acceptability of palliative care as an intervention among LT-LVAD patients, it will inform the development of a large, randomized trial to test efficacy of palliative care for LT-LVAD recipients. If palliative care is demonstrated to be effective at improving HRQoL in LT-LVAD patients, this will revolutionize the post-LVAD treatment paradigm by integrating palliative care specialists into the longitudinal care of LT-LVAD patients. The scope of impact of this project is expected to be the thousands of patients who are living with LT-LVAD and may receive this technology and its subsequent iterations in the future.
PRELIMINARY STUDIES Our retrospective study conducted at MHVI examining 233 LT-LVAD patients who underwent implant between 2017 and 2021 (published in Journal of Cardiac Failure) demonstrated that LT-LVAD patients in our cohort experience a high burden of medical complications, hospitalizations and time spent in-hospital for acute illness. Despite the burden and toll exerted by these medical complications (psychosocially and physically), only 34% of the patients in this real-world cohort received outpatient palliative care (OPC). Importantly, this study demonstrated that time to first OPC encounter is on average 12 months prior to death, suggesting that patients are only referred to OPC later in their disease course, and therefore have less time to benefit from OPC services.
The investigators have completed baseline HRQoL assessments for 15 LT-LVAD patients at MHVI over the span of 5 weeks using the scales to be collected in Aim 1 (Table) addressing multiple domains of HRQoL. Thus far, of 15 patients interviewed, one-third were female and 73% identified as Black race with median age of 72 years. Average KCCQ-12 score was 55.5 (SD 8.0), EQ-5D 8.8 (SD 3.4) and FACIT-Pal 42.3 (SD 8.1). This preliminary data has demonstrated that patients are willing to participate in this type of study and that the study institution has the expertise and resources to conduct the proposed study.
METHODS Aim 1: The investigators will include patients older than 18 years of age on LT-LVAD support (not anticipated to be considered for HT given non-modifiable barriers to transplant candidacy). Patients who are being evaluated for, listed for, or who have received HT will be excluded. The investigators will collect items including KCCQ-12, EQ-5D, FACIT-Pal-14 (to assess self-reported quality of life through several domains including physical well-being, social/family well-being, emotional well-being, and functional well-being), Hospital Anxiety and Depression Scale (HADS), IES-6, which measures burden of post-traumatic stress disorder symptoms, MCS A-QOL 20, which measures specific burdens of LVAD therapy and satisfaction with LVAD therapy, FACIT-Sp-12, which measures spiritual/existential distress, and the FACIT-TS-G scale, which measures treatment satisfaction/burden, from a cross-section of patients with LT-LVAD. Altogether these assessments take approximately 45-60 minutes to be administered with assistance from a research assistant. By comparing the responses to these scales and controlling for confounders such as adverse medical complications (chronic infections, recurrent hospitalizations, etc.) using standard regression or proportional odds models, the investigators aim to characterize HRQoL of the overall cohort and understand differences among subgroups such as women and Black patients living with LVAD.
Aim 2: This aim consists of a randomized, unblinded pilot study of a palliative care intervention for patients living with LVAD therapy. The investigators will offer randomization of patients assessed by Aim 1 who have not received outpatient palliative care services in the preceding 6 months into the trial. The usual care arm will consist of routine LVAD care with clinician-triggered referral for palliative care specialist evaluation. The palliative care arm mirrors the intervention described in a cohort of patients with HF in the PAL-HF trial. The intervention will be conducted by a palliative care specialist nurse practitioner (NP) with standardized training in administering the intervention. The NPs will conduct visits approximately every 6 weeks with the patient. The patient will be referred for interdisciplinary supportive care from the palliative care chaplain, social worker, and/or pharmacist based on NP evaluation. Additionally, based on baseline clinical assessment scales and symptoms, patients will be offered supportive medications or referrals for cardiac rehabilitation and behavioral health/psychiatry. Data regarding interventions (including referrals, medication orders or other specific counseling) will be abstracted from the NP's clinic documentation. After 6 months from the initial palliative care evaluation, the above HRQoL scales will be repeated for the patients in both arms. Each instrument corresponds to specific HRQoL domains that may be impacted by possible interventions listed in the Table. The feasibility and acceptability of this intervention will be assessed by surveying participants (patients and providers) regarding their views on the pilot. For this, the investigators will conduct a mixed-methods analysis using quantitative surveys and qualitative interviews.
ANALYSIS PLAN
Aim 1 will be analyzed using descriptive and inferential statistics. The investigators aim to recruit ~50% of all patients at each study site on LT-LVAD support meeting study criteria (a cross-section of ~150 patients). The investigators will collaborate with experienced biostatisticians from MedStar Health Center for Biostatistics, Informatics, and Data Science (CBIDS). Standard regression or proportional odds models (all ordinal outcomes and any outcome that is skewed) will be used to study associations between HRQoL outcomes and patient demographics and medical complications. The KCCQ, for instance, is a disease specific questionnaire scored from 0 to 100, with high scores representing better health status. The investigators will use univariate regressions to estimate the potential for any demographic variables or medical complications to increase the likelihood of worse KCCQ scores. All factors having large, estimated odds ratios will be evaluated for feasibility in stratified sampling for the subsequent randomized prospective trial.
Aim 2 will assess the feasibility and acceptability of the proposed intervention. The investigators will recruit and randomize 45 patients into each arm for this pilot study. This study is not powered to test for changes in the primary outcome of improvement in HRQoL. The feasibility and acceptability of this standardized intervention will be the primary objective of Aim 2. The RE-AIM framework will be used to inform the assessment of whether patients and providers found the intervention to be acceptable. Feasibility outcomes will be measured by intervention enrollment numbers, retention, and follow up over the course of the 6-month intervention. The investigators will quantify how many patients receive supportive medications or referrals to members of the palliative care interdisciplinary team (social worker, chaplain and pharmacist), behavioral health, and cardiac rehabilitation. The rates of follow-up with these ancillary services will be assessed. Readmission rates in both arms will be compared. To study acceptability, the investigators will conduct surveys with patients examining their perspectives on the intervention. The investigators will use Likert scale-based survey tools and conduct individual semi-structured interviews with patients in the intervention arm to understand their views on the barriers/facilitators and the need for additional adaptation or refinement of the intervention and its assessment prior to implementation on a wider scale.
The data management plan for this study will include creation and maintenance of a REDCap database. The study team has expertise in coordinating with CBIDS bioinformaticists to generate and implement the REDCap database.
Upon completion of this project, the investigators will have generated the evidence needed to power a study of efficacy of a structured, prospective palliative care intervention with the objective of improving HRQoL for patients living with LT-LVAD. The investigators will use the pilot to further refine the study protocol, intervention/standard of practice, randomization and informed consent processes, and needed infrastructure for a larger randomized controlled trial.
Inclusion Criteria:
Exclusion Criteria:
richa.gupta@medstar.net202-877-4698
anirudh.rao@inova.org703-776-4289