The experiences among bereaved family members after a left ventricular assist device (LVAD) deactivation.

BACKGROUND: The use of left ventricular assist devices (LVADs) is increasing with an estimated 2500 devices implanted each year. When burdens of the LVAD outweigh benefits, most individuals with LVADs will undergo deactivation in the hospital setting. While the decision to deactivate an LVAD is considered an ethical practice, little is known about the experience and needs of bereaved family members. OBJECTIVE: To investigate the experiences of bereaved family members of patients who died following LVAD deactivation. METHODS: In this qualitative study, 11 family members of patients who underwent LVAD deactivation were interviewed. The semi-structured interviews were conducted until data saturation was reached and relevant themes emerged. RESULTS: This qualitative study was conducted to understand the experience of family members before, during and after the patient underwent LVAD deactivation, including their perceptions of engagement with the healthcare team. Analysis revealed six overarching themes from the experience, including 1) hope for survival, 2) communication, 3) spirituality and faith, 4) absence of physical suffering, 5) positive relationships with staff, 6) post-death care needs. CONCLUSION: Bereaved family members of patients undergoing LVAD deactivation have unique lived experiences and concerns. This study highlights the importance of effective communication not only near end-of-life but throughout the LVAD experience. While the positive relationships with staff and the absence of physical suffering were strengths identified by bereaved caregivers, there is an opportunity for improvement, particularly during the decision-making and post-death periods.

Disease-State Understanding and Experience of Patients Receiving Continuous Intravenous Inotropic Support as Palliative Therapy: A Multicenter Survey.

Background: The use of continuous intravenous inotropic support (CIIS) as palliative therapy in patients with advanced heart failure (HF) has increased over the past decade. CIIS improves New York Heart Association (NYHA) functional class but does not impact survival. Objective: The objective of this study was to examine patients' understanding of the therapeutic intent of CIIS, prognostic awareness, and quality of life with CIIS. Design: We conducted a prospective, cross-sectional, multicenter study of patients with advanced HF receiving CIIS as palliative therapy between 2020 and 2022. Settings/Subjects: An investigator-developed survey instrument was administered to outpatients on CIIS in the United States via telephone. Measurements: Survey data were analyzed using descriptive and inferential statistics. Results: Forty-eight patients, 63% male, 81% African American/Black, with a mean age of 68.9 (standard deviation 12.3) years, participated in this study. The majority of patients responded that they expected CIIS to make them feel better (79%) and increase longevity (75%), but few expected that CIIS would cure their HF (19%). Patients described their overall quality of life on CIIS as not better/worse (19%), somewhat better (46%), and significantly better (35%) and reported high treatment satisfaction (87% were at least somewhat satisfied). Conclusions: In this study, patients report improved quality of life with CIIS as palliative therapy. Patients on CIIS as palliative therapy expected increased survival on CIIS, which is incongruent with current evidence. Further studies on how we can improve care processes so that patients have accurate prognostic and disease-state awareness, and receive goal concordant care, are warranted.

The current use of proteomics and metabolomics in glomerulonephritis: a systematic literature review.

BACKGROUND: Glomerulonephritis inherently leads to the development of chronic kidney disease. It is the second most common diagnosis in patients requiring renal replacement therapy in the United Kingdom. Metabolomics and proteomics can characterise, identify and quantify an individual's protein and metabolite make-up. These techniques have been optimised and can be performed on samples including kidney tissue, blood and urine. Utilising omic techniques in nephrology can uncover disease pathophysiology and transform the diagnostics and treatment options for glomerulonephritis. OBJECTIVES: To evaluate the utility of metabolomics and proteomics using mass spectrometry and nuclear magnetic resonance in glomerulonephritis. METHODS: The systematic review was registered on PROSPERO (CRD42023442092). Standard and extensive Cochrane search methods were used. The latest search date was March 2023. Participants were of any age with a histological diagnosis of glomerulonephritis. Descriptive analysis was performed, and data presented in tabular form. An area under the curve or p-value was presented for potential biomarkers discovered. RESULTS: Twenty-seven studies were included (metabolomics (n = 9)), and (proteomics (n = 18)) with 1818 participants. The samples analysed were urine (n = 19) blood (n = 4) and biopsy (n = 6). The typical outcome themes were potential biomarkers, disease phenotype, risk of progression and treatment response. CONCLUSION: This review shows the potential of metabolomic and proteomic analysis to discover new disease biomarkers that may influence diagnostics and disease management. Further larger-scale research is required to establish the validity of the study outcomes, including the several proposed biomarkers.

The role of palliative care for patients with left ventricular assist devices: a narrative review.

BACKGROUND AND OBJECTIVE: Left ventricular assist devices (LVADs) have revolutionized the care of patients with advanced heart failure (HF). Compared to guideline-directed medical and device therapies, LVAD technology improves quality of life and reduces mortality. Palliative care specialists have an important role to play in the pre-LVAD evaluation phase, in the post-operative longitudinal care phase, and at the endof-life in patients with LVADs. The objective of this narrative review is to describe the evidence regarding the role of palliative care for patients with LVAD across the care continuum: pre-implantation, postimplantation, and at the end-of-life. METHODS: Clinical trials relevant to care of patients with HF, LVADs, and the role of palliative care were analyzed for this narrative review. KEY CONTENT AND FINDINGS: Palliative care involvement in 'preparedness planning' has been described in the literature, though no standardized protocol for preparedness planning exists, to date. In the longitudinal care phase after LVAD implantation, the role of palliative care is less defined; depending on institutional culture and availability of palliative care, patients may be referred based on symptom-management needs or for advance care planning (ACP). At the end-of-life, either due to an acute event or a gradually worsening condition, palliative care is often engaged to participate in discussions regarding treatment preferences and to consider transitions in care from disease-directed treatments to comfort-focused treatments. Given the medical complexity of dying with LVADs, most patients with an LVAD die in hospital with support from palliative care teams for the physical, existential, and psychosocial distress that accompanies end-of-life and LVAD deactivation. CONCLUSIONS: In this narrative review, we describe the integral role of palliative care throughout the care continuum of patients living with LVADs and suggest opportunities for further research.

The Complex Ethical and Moral Experience of Left Ventricular Assist Device Deactivation.

The left ventricular assist device (LVAD) is a fully implantable cardiac replacement device that can complicate the process of dying. We present a case of a patient who attempted to deactivate the LVAD without the support of his medical team. This action was understood as a "suicide attempt" though when the patient was later felt to be dying, LVAD deactivation proceeded without reference to psychiatric illness. To understand this case, we discuss the ethics of LVAD deactivation in the dying process. We then explore the experience of clinicians and the public encountering this unique technology across clinical contexts. We herein present a novel and possibly controversial analysis of the moral complexities of LVAD deactivation and suggest that clinicians be transparent about these complexities with patients and families.

Benefits and Harms of Continuous Intravenous Inotropic Support as Palliative Therapy: A Single-Institution, Retrospective Analysis.

Use of continuous intravenous inotropic support (CIIS) strictly as palliative therapy for patients with ACC/AHA Stage D (end-stage) Heart Failure (HF) has increased significantly. The harms of CIIS therapy may detract from its benefits. To describe benefits (improvement in NYHA functional class) and harms (infection, hospitalization, days-spent-in-hospital) of CIIS as palliative therapy. Methods: Retrospective analysis of patients with end-stage HF initiated on CIIS as palliative therapy at an urban, academic center in the United States between 2014-2016. Clinical outcomes were extracted, and data were analyzed using descriptive statistics. Seventy-five patients, 72% male, 69% African American/Black, with a mean age 64.5 years (SD = 14.5) met study criteria. Mean duration of CIIS was 6.5 months (SD = 7.7). Most patients (69.3%) experienced improvement in NYHA functional class from class IV to class III. Sixty-seven patients (89.3%) were hospitalized during their time on CIIS, with a mean of 2.7 hospitalizations per patient (SD = 3.3). One-third of patients (n = 25) required at least one intensive care unit (ICU) admission while on CIIS therapy. Eleven patients (14.7%) experienced catheter-related blood stream infection. Patients spent an average of 20.6% (SD = 22.8), approximately 40 days, of their time on CIIS admitted to the study institution. Patients on CIIS as palliative therapy report improvement in functional class, survive 6.5 months following initiation, but spend a significant number of days in the hospital. Prospective studies quantifying the symptomatic benefit and the direct and indirect harms of CIIS as palliative therapy are warranted.

PLA2R Antibody Does Not Outperform Conventional Clinical Markers in Predicting Outcomes in Membranous Nephropathy.

Introduction: The prognostic value of PLA2R antibody (Ab) test in clinical practice remains unclear. We aimed to evaluate its ability in predicting hard outcomes in primary membranous nephropathy (PMN) after adjustments to conventional markers of disease activity. Methods: A total of 222 patients diagnosed with PMN from January 2003 to July 2019 having had a serum PLA2R Ab test, were included from 3 centers in the north of England. Baseline conventional markers, PLA2R-Ab-status (positive vs. negative), Ab-titer (high vs. low), and time of testing (pre-PLA2R era vs. PLA2R era) were evaluated for association with outcomes. Primary outcome was time to progression (composite of doubling of creatinine, stage 5 chronic kidney disease, or death). Secondary outcomes were time to partial remission (PR) and time to immunosuppression. Cox proportional hazard testing was used. Results: During a median follow-up of 5.26 years, progression was seen in 65 (29.3%) and PR in 179 of 222 patients (80.6%). There was a clear association of estimated glomerular filtration rate (eGFR) (standardized hazard ratio [HRZ] = 0.767, P < 0.05) and urine protein-to-creatinine ratio (uPCR) (HRZ = 1.44, P < 0.005) with time to progression among all patients, and eGFR (HRZ = 0.606, P < 0.005) in Ab-positive patients. Baseline Ab-positivity was not associated with time to progression (adjusted hazard ratio [aHR] = 0.93, P = 0.71) or time to PR (aHR = 0.84, P = 0.13). Similarly, baseline high Ab-titer was not associated with time to progression (aHR = 1.07, P = 0.77) or time to PR (aHR = 0.794, P = 0.08). Conclusion: Once adjusted to conventional markers of disease activity, baseline PLA2R Ab-positivity or Ab-titer do not predict disease progression or time to PR. Further studies are needed to harness the utility of PLA2R Ab test in prognostication in PMN.

Determinants of Health and Outcomes in Medicare Recipients With Heart Disease: A Population Study.

CONTEXT: Heart disease (HD) is a primary cause of mortality and morbidity in the United States. While there is a growing body of evidence demonstrating the contribution of social determinants of health (SDoH) to HD outcomes, the impact of combined or individual SDoH on health-related quality of life (HRQoL) in patients with HD is not well understood. OBJECTIVES: To analyze the National Health and Aging Trends Study (NHATS) to explore the relationship of SDoH with HRQoL, advance care planning, and treatment preferences in Medicare beneficiaries with HD. METHODS: The study design was a secondary data analysis using latent class analysis (LCA) and multivariable analysis of NHATS participants with HD, Round 8, that included End of Life Plans and Care questions. RESULTS: 1202 participants, median age 81 years, 57% female, 70% non-Hispanic White, 20% non-Hispanic Black, 10% Other. LCA identified two SDoH risk profiles (low/high), using 12 measures within the NHATS Economic and Social Consequences key concept area. The high-risk SDoH profile participants were more likely to have fair/poor HRQoL, and identify as female, non-White (P < 0.0001); and less likely to have completed advance care planning (P < 0.0001). High-risk SDoH participants were more likely to want life-prolonging treatments (P < 0.0001), however, this association was not significant after adjusting for age, sex, and race (P = 0.344). CONCLUSION: Higher risk SDoH profiles are associated with reduced HRQoL, reduced advance care planning completion, female sex, and non-White race in a cohort of Medicare beneficiaries. These findings provide opportunities to improve SDoH-related care practices in older patients with HD.

Clinical Protocol for Left Ventricular Assist Device Deactivation at End of Life.

As patients live longer with left ventricular assist device (LVAD) support, many will either suffer an acute event or develop a gradual, progressive disease that results in a terminal prognosis. At the end-of-life, patients, and more often, their families, will be faced with the decision to deactivate the LVAD to allow natural death. The process of LVAD deactivation carries some distinct features that distinguish it from withdrawal of other forms of life-sustaining medical technology: multidisciplinary collaboration is paramount; prognosis after deactivation is short, typically minutes-hours; and premedication doses of symptom-focused medications are typically higher than other situations involving withdrawal of life-sustaining medical technologies given the precipitous decline in cardiac output following LVAD deactivation. In this Case Discussion, we introduce the complexity of planned in-hospital LVAD deactivation through a clinical case, share our detailed institutional checklist and order set for LVAD deactivation, and broach multidisciplinary clinical protocol development processes.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

INTRODUCTION: We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. METHODS: A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020. Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. RESULT: 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9 year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

Association Between Patient Race and Ethnicity and Outcomes With COVID-19: A Retrospective Analysis From a Large Mid-Atlantic Health System.

BACKGROUND: Members of racial and ethnic minority groups have been disproportionately impacted by coronavirus-2019 (COVID-19). The objective of the study is to describe associations between race and ethnicity on clinical outcomes such as need for mechanical ventilation and mortality. METHODS: Retrospective cohort study of patients with severe COVID-19 infection admitted within a large, not-for-profit healthcare system in the mid-Atlantic region between March and July, 2020. Patient demographic data and clinical outcomes were abstracted from the electronic health record. Logistic regressions were performed to estimate associations between race and ethnicity and the clinical outcomes. RESULTS: The study population (N = 2931) was stratified into 1 of 3 subgroups: non-Hispanic White (n = 466), non-Hispanic Black (n = 1611), and Hispanic (n = 654). The average age of White, Black, and Hispanic patients was 69 ± 17.06, 64 ± 15.9, and 50 ± 15.53 years old, respectively (P < .001). Compared to White patients, Black and Hispanic patients were at increased odds of needing mechanical ventilation due to COVID-19 pneumonia (odds ratio [OR] Black = 1.35, 95% confidence interval [CI] = 1.04 to 1.75, P < .05; OR Hispanic = 1.43, 95% CI = 1.06 to 1.93, P < .05). When compared to White patients, Hispanic patients were at decreased odds of death (OR = 0.45, 95% CI = 0.32 to 0.63, P < .001). However, when adjusting for age, there were no statistically significant differences in the odds of death between these groups (adjusted OR [aOR] Black = 1.05, 95% CI = 0.80 to 1.38, P = .71; aOR Hispanic = 1.10, 95% CI = 0.76 to 1.60, P = .62). CONCLUSION: Our analysis demonstrated that Hispanic patients were more likely require mechanical ventilation but had lower mortality when compared to White patients, with lower average age likely mediating this association. These findings emphasize the importance of outreach efforts to communities of color to increase prevention measures and vaccination uptake to reduce infection with COVID-19.

SARS-CoV-2 in dialysis patients and the impact of vaccination.

BACKGROUND: In centre haemodialysis (ICHD) patients have been identified as high risk of contracting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection due to frequent healthcare contact and poor innate and adaptive immunity. Our ICHD patients were offered immunisation from January 2021. We aimed to assess outcomes following SARS-CoV-2 infection and report on the effect of vaccination in our ICHD patients. METHODS: Demographics, SARS-CoV-2 status, hospitalisation, mortality and vaccination status were analysed. From 11th March 2020 to 31st March 2021, 662 ICHD patients were included in the study and these patients were then followed up until 31st August 2021. RESULTS: SARS-CoV-2 infection occurred in 28.4% with 51.1% of them requiring hospitalisation in contrast to community infection rates of 13.9% and hospitalisation of 9.0%. 28-day mortality was 19.2% in comparison to 1.9% of the community. Mortality increased to 34.0% over the study period. Mortality over the study period was 1.8 times in infected patients (HR 1.81 (1.32-2.49) P < 0.001) despite adjustment for age, gender and ethnicity. 91.3% of ICHD patients have now received both doses of SARS-CoV-2 vaccinations. CONCLUSIONS: ICHD patients are at increased risk of acquiring SARS-CoV-2, with increased rates of hospitalisation and mortality. The increased mortality extends well beyond the 28 days post-infection and persists in those who have recovered. Peaks and troughs in infection rates mirrored community trends. Preliminary data indicates that the SARS-CoV-2 vaccination provides protection to ICHD patients, with ICHD case rates now comparable to that of the local population.

Bridge to nowhere: A retrospective single-center study on patients using chronic intravenous inotropic support as bridge therapy who do not receive surgical therapy.

Background: Many patients with advanced heart failure (HF) are administered chronic intravenous inotropic support (CIIS) as bridge to surgical therapy; some ultimately never receive surgery. We aimed to describe reasons patients "crossover" from CIIS as bridge therapy to palliative therapy, and compare end-of-life outcomes to patients initiated on CIIS as palliative therapy. Methods: Single-institution, retrospective cohort study of patients on CIIS as bridge or palliative therapy between 2010 and 2016; data obtained through review of health records and multi-disciplinary selection meeting minutes, was analyzed using descriptive and inferential statistics. Results: Of 246 patients discharged on CIIS as bridge therapy, 37 (16%) (male n = 28, 76%; African American n = 22, 60%) ultimately never received surgery. 67 matched patients on CIIS as palliative therapy were included for analysis (male n = 47, 70%; African American n = 47, 70%). The most common reasons for "crossover" from CIIS as bridge therapy to palliative therapy were frailty (n = 10, 27%), cardiac arrest (n = 5, 13.5%), and progressive non-cardiac illnesses (n = 6, 16.2%). A similar percentage of patients in the bridge (n = 28, 76%) and palliative (n = 48, 72%) groups died outside the hospital (P=0.66); however, fewer bridge patients received hospice care compared to the palliative group (35% vs 69%, P < 0.001). Comparing patients who died in the hospital, bridge patients (n = 9; 100%) were more likely to die in the intensive care unit than palliative patients (n = 8; 42%) (P < 0.001). Conclusion: Patients on CIIS as bridge therapy who do not ultimately receive surgical therapy "crossover" to palliative intention due to frailty, or development of or identification of serious illnesses. Nevertheless, these "bridge to nowhere" patients are less likely to receive palliative care or hospice and more likely to die in the intensive care unit than patients on CIIS as palliative therapy.

In-Hospital Left Ventricular Assist Devices Deactivation and Death Experience: A Single-Institution Retrospective Analysis.

Best practices for left ventricular assist devices (LVADs) deactivation at end-of-life (EOL) have yet to be elucidated. We conducted a single-institution retrospective review of patients who died following LVAD deactivation between January 2017 and March 2020. Data were obtained from institutional databases and electronic health record and were analyzed using descriptive statistics. Fifty-eight patients (70% male, 70% African American, median age 62 years) were categorized by implant strategy: bridge therapy (BT, N = 22, 38%) or destination therapy (DT, N = 36, 62%). Clinical events leading to deactivation were categorized either acute ( e.g. , stroke [ N = 31, 53%]), gradual decline ( N = 12, 21%), or complications during index hospitalization ( N = 15, 26%). Implant strategy was not associated with clinical trajectory leading to EOL ( p = 0.67), hospital unit of death ( p = 0.13), or use of mechanical ventilation ( p = 0.69) or renal replacement therapy ( p = 0.81) during terminal hospitalization. Overall time from admission to code status change was mean 27.0 days (SD 30.3 days). Compared with BT patients, DT experienced earlier do-not-resuscitate (DNR) orders ( p ≤ 0.01) and shorter survival post-deactivation ( p ≤ 0.01). Deactivations after gradual decline tended to occur outside ICUs, compared with acute events or index implant-related complications ( p = 0.04). Implant strategy was not associated with differences in EOL experience except regarding timing of DNR order and survival post-deactivation.

Continuous Intravenous Inotropic Support for Advanced Heart Failure: Palliative Considerations.

The global prevalence of heart failure (HF) is increasing. Advancements in guideline-directed medical and device therapy have resulted in improved survival. Thus, there are more patients living - and living longer - with advanced HF. Only a small proportion of these patients are deemed appropriate for advanced surgical intervention (mechanical circulatory support or heart transplantation), and even if offered, some may decline such interventions if not aligned with their overall goals and values. Therefore, a growing number of patients with advanced HF receive chronic intravenous inotropic support (CIIS) for palliation of symptoms. Despite increased use, clinical evidence supporting use of palliative inotropes remains limited. However, available data suggest improvements in functional class, health-related quality of life (HRQoL) indicators, symptom burden, hemodynamic parameters, and possibly rehospitalization. While initial concerns regarding increased mortality have been assuaged in the modern era of guideline-directed medical therapy, palliative inotropes are certainly not without burden. Risks of infection and medication-related adverse effects, need for routine laboratory monitoring, frequent dressing changes, and presence of a reliable caregiver must be carefully considered prior to initiation. This review addresses pharmacology, guideline recommendations, benefits and burdens, considerations related to hospice and end-of-life care, and future directions of CIIS in advanced HF care.

Alemtuzumab in renal transplantation. Reviews of literature and usage in the United Kingdom.

Kidney transplantation has evolved over the years from transplants between identically matched donors and recipients to successfully transplanting allografts across virtually any degree of donor-recipient human leukocyte antigen mismatch and ABO-incompatibility. Integral to these improved outcomes has been the development and deployment of a range of immunosuppressive agents. The addition of monoclonal and polyclonal antibodies as a standard part of overall immunosuppression has led to the improved outcomes by providing a robust and focused protection during the first few months of transplantation when allografts are most vulnerable to immune-mediated injury. Alemtuzumab is a recombinant anti-CD52 pan-lymphocyte depleting monoclonal antibody that has been in use for kidney transplantation since the late 1990s. Despite the many years of experience with alemtuzumab, its utilisation in the UK has remained relatively restrained. This may be due to a lack of high-level evidence to support its safety and efficacy in transplantation. Also, long-term outcomes have not been addressed by existing studies. Nevertheless, available evidence suggests that alemtuzumab is associated with a lower risk of acute rejection within the first year of transplantation while exhibiting a comparable safety profile to non-lymphocyte depleting agents. Despite the current economic advantages of alemtuzumab (available free of cost on a named transplant recipient basis), its use in UK transplant centres has remained limited, variating from non-use, through usage in selected high immunologic risk subjects, to use as routine induction immunosuppression. This review discusses the current use of alemtuzumab for immunosuppression induction in kidney transplantation. It describes its evolution from development to its present application in kidney transplantation and reviews the evidence underpinning its utilisation. The role of alemtuzumab in the immunosuppressive protocols individual UK kidney transplant centres is also described.