Swetz, Keith M.

Abstract Rationale Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. Objectives To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain. Methods At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain. Measurements and Main Results Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20–96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14–36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). Conclusions Chronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible “second hits” that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

Background: Heart failure (HF) is a clinical syndrome with an overall poor prognosis, but the clinical trajectory is often unpredictable in individuals. There has been an impetus to promote iterative patient-provider discussions regarding preferences for end of life (EOL) care and advanced care planning. However, very little is known regarding provider preferences or their personal confidence addressing EOL care with their patients with HF. To address these gaps in knowledge, we surveyed clinicians at three practice sites in a large integrated health system. Methods: Physicians, nurse practitioners (NP), and physician assistants (PA) at Mayo Clinic (Rochester, Minnesota) and its surrounding health system were asked to participate in an electronic survey in October 2013. Clinicians surveyed included tertiary care HF specialists (Tertiary Care Cardiology), cardiologists and NP/PAs practicing in a community setting (Community Cardiology), and primary care clinicians (Primary Care). Results: A total of 95 clinicians completed the survey (52.5% response rate), including 50 physicians and 45 NP/PAs. Clinicians reported discussing prognosis and EOL wishes when their patient’s health status was worsening, but only 12% reported annual discussions as advocated by the American Heart Association. In total 52% of providers reported one or more reasons that they hesitate to discuss EOL care with their patients, including provider discomfort (11%), perception of patient (21%) or family (12%) unreadiness to have the discussion, fear of destroying hope (9%), or a lack of time (8%). Tertiary Care (63%) and Community Cardiology (58%) clinicians were more likely to attribute responsibility for having EOL discussions to the HF cardiologist, while 66% of Primary Care providers felt it was their responsibility. Tertiary and Community Cardiology clinicians were more likely to have referred patients to Palliative Medicine within the last year than Primary Care (89% vs. 21%, p<0.001). Overall, 30% of those surveyed reported low or very low confidence levels in initiating prognosis or EOL discussions, enrolling patients in hospice, or providing EOL care, with lower confidence among those with fewer years of clinical experience. The majority of clinicians expressed a high level of interest in further skills acquisition on these topics. Conclusion: There is tremendous variability in the way that clinicians view and approach advanced care discussions with their patients with HF; varying provider perception and lack of provider confidence may contribute. Despite this variability, most clinicians are interested in further development and skills acquisition. Addressing the learning needs of providers is an important next step toward enhancing the EOL care of patients with HF.

BACKGROUND: Destination therapy left ventricular assist device (DT LVAD) is increasingly offered to patients with end-stage heart failure who are ineligible for heart transplantation. Implanting centers often require the identification of a dedicated caregiver prior to DT LVAD implantation; however, the caregiver experience surrounding this difficult decision is relatively unexplored. METHODS: Between October 2012 and July 2013, we conducted semi-structured, in-depth interviews of caregivers to understand their experiences with decision making for loved ones considering and living with DT LVADs. Data were analyzed using a mixed inductive and deductive approach. RESULTS: We interviewed 17 caregivers: 16 caregivers of patients who had received a DT LVAD and 1 caregiver of a patient who had declined a DT LVAD. At the time of the caregiver interview, 10 DT LVAD patients were living and 7 were deceased. The majority were women (n=16) of whom 12 were either spouses or widows of the patients. Median age of caregivers was 65 (range 35-79). Twelve caregivers reported spending more than 8 hours per week caring for their loved one, and 14 attended regular medical appointments. Throughout the interviews, caregivers reported that DT LVAD was a complex decision making process with many inherent tensions. The themes identified are broadly interpreted under three domains: 1) the stark decision context with tension between hopes and realities, “when we first started out¼we had hopes of a transplant¼but once the lung function was done, and the kidneys ¼there was pretty much nothing. There was no hope other than the LVAD”; 2) the challenging decision process and the tension between wanting their loved ones to live, “I said ‘Well, I'll tell you what. I didn't marry you to be a young widow” and wanting to respect their loved ones’ wishes, “My thoughts were this was his life and it was his choice”; and 3) the downstream decision outcome and the tension between gratitude, “I'm just thankful to have my dad here¼” and a feeling of burden, “I've never felt caregiver was my gift¼I tend to feel like I'm being imposed upon at times.” CONCLUSIONS: Despite the promise of significantly improved survival for some patients, DT LVAD has major implications for caregives as well as patients. Decision making surrounding DT LVAD requires education of both the patient and caregiver of potential stresses. Additionally, decision-making surrounding DT LVAD should seek to incorporate decision support for patients and caregivers. This should include a focus on caregiver burden and the tensions that caregivers may experience.

Background: Left ventricular assist devices as destination therapy (DT-LVAD) have been shown to decrease mortality compared with medical management, and can improve quality of life for many patients with advanced heart failure. However, while most patients live longer with DT-LVAD than they would have with medical therapy, deaths still occur. We sought to systematically examine the end-of-life care of patients who died with a DT-LVAD at a single center. Methods: All patients undergoing DT-LVAD at the Mayo Clinic in Rochester, Minnesota from January 1, 2007 through September 30, 2014 who subsequently died prior to July 1, 2015 were included. The cause of death was determined based on review of documentation in the electronic medical record, including autopsy reports, death certificates and clinical notes. Details about palliative care consultations, hospice enrollment, hospitalizations, and device deactivation at the end-of-life were obtained from the electronic medical record. Results: Of 89 patients that died with a DT-LVAD (84 HeartMate II, 3 HeartWare, 2 Heartmate XVE, mean age at death 66.1 years), the mean (standard deviation) time from LVAD implantation to death was 2.0 (1.9) years. The most common causes of death were multiorgan failure (25.9%), hemorrhagic stroke (24.7%), and progressive heart failure (20.0%). Nearly half (45.6%) of patients saw palliative care in consultation within a month prior to death. However, only 13 (15.5%) patients enrolled in hospice a median of 11 (range 1-315) days prior to death, including 4 patients with concurrent cancer, 2 with stroke, and 7 with multiorgan failure. The vast majority of patients (78.6%) died in the hospital, and of those hospitalized at death, 87.7% died in the intensive care unit. Most patients hospitalized at death transitioned to a comfort-directed approach to care within 24 hours of dying. In total, 43 (48.3%) patients had their LVAD deactivated prior to death, with all but 3 undergoing deactivation in the hospital. The vast majority of patients died within an hour of LVAD deactivation, and all within 26 hours. Conclusions: In contrast to the general heart failure population, most patients with DT-LVAD die in the hospital and very few enroll in hospice. A significant body of research has demonstrated that patients who die in the intensive care unit and the hospital, as opposed to home or with hospice assistance, experience worse quality of life, quality of death and caregiver outcomes. Potential reasons that patients with DT-LVAD may experience different end-of-life care than other patients with heart failure exist, including that they often experience sudden changes in health status prior to death from acute events such as hemorrhagic stroke. However, further work is needed to understand these differences and to determine whether patients with DT-LVAD are receiving optimal end-of-life care.

Background: Destination therapy left ventricular assist devices (DT-LVADs) have become a treatment option for carefully selected patients with end-stage heart failure. Death is inevitable despite DT-LVAD, with 1-year mortality approximately 20% and median survival 5 years. However, end-of-life processes for LVAD patients vary significantly by institution, provider, and patient preference. Palliative care has played an increasing role in the care of this patient population, yet there remains little data on the most effective way to integrate palliative care and hospice in the DT-LVAD population. Therefore, we aimed to understand the end-of-life perspectives regarding LVADs among both cardiology and palliative care/hospice providers. Methods: Using internet-based, secure methods, we administered a 41-item survey via electronic mail to members of the American Academy of Hospice and Palliative Medicine, European Society of Cardiology-Heart Failure Association, the International Society for Heart and Lung Transplantation, and the Heart Failure Society of America to assess their perspectives on end-of-life care in patients with LVADs. Descriptive statistics were used to analyze data. Fisher’s exact test was used to compare categorical data. Results: From October to November 2011, there were a total of 440 respondents (palliative care/hospice=137; cardiology=303). Most were physicians (80%; n=320) and male (59%; n=232). The majority of providers in both groups viewed an LVAD as a life-sustaining treatment. The groups differed in their attitudes, beliefs, and comfort with end-of-life care in patients with an LVAD. Few palliative care/hospice providers believed a patient needed to be imminently dying to turn off an LVAD; whereas most cardiology providers noted patients should be imminently dying in order to consider LVAD deactivation (2% vs 60%; p=<0.001). Most palliative care/hospice providers believed requests for turning off an LVAD in a patient who is not nearing death should be honored. In contrast, just over half of cardiology providers contended the request should be honored (88% vs 57%; p=<0.001). The provider groups also disagreed on requiring ethics consultation, with most cardiology providers stating it was necessary prior to turning off an LVAD near the end of life (67% vs 24%; p=<0.001). Conclusion: Cardiology providers and palliative care/hospice providers collectively have different perceptions on management of end of life in patients with an LVAD. Bridging the gaps between these two disciplines is a critical first step in creating a more cohesive approach to end-of-life care for these patients—one that honors autonomy but respects individual provider comfort levels.

Background: Heart failure (HF) has an overall poor prognosis, with only half of patients surviving more than 5 years after diagnosis. Although it is recommended that all patients with HF have advance directives (ADs) in place before the end of life is imminent, the use of ADs in these patients has not been well studied. Methods: We prospectively enrolled all Olmsted County residents presenting with active HF from October 2007 through October 2011 into a longitudinal community cohort study which included an echocardiogram and administration of health status questionnaires at enrollment. Information from ADs completed prior to enrollment was manually abstracted from the patient’s medical record. Results: A total of 608 patients were enrolled during the study period (mean age 74.0 years, 54.9% male, 49.9% with preserved EF [EF≥50%], 65.3% NYHA functional class 3 or 4). Mortality was high; 164 (27.0%) patients died after a mean follow-up of 1.8 years with estimated 1-year mortality of 14.3%. At the time of enrollment, only 249 (41.0%) patients had ADs, and they were completed an average of 3.3 years prior. Although most ADs appointed a proxy decision-maker (91.1%), less than half addressed patient wishes regarding use of cardiopulmonary resuscitation (41.4%), mechanical ventilation (38.7%), administration of artificial nutrition (38.6%), or hemodialysis (10.0%) at the end of life. AD use was more common in older individuals (p<0.001); 60.7% of those ≥80 years had an AD vs. 13.6% of those who were <60 years old. While ADs were more common in women than men (46.7% vs. 36.2%, respectively) and in those with preserved EF (47.2% vs. 34.0% in those with reduced EF), differences were not significant after adjustment for age. AD use was no more common in patients with worse NYHA functional class or health status as measured by the Kansas City Cardiomyopathy Questionnaire. Conclusions: Despite a high mortality rate, over half of community patients with HF do not have ADs, and existing AD fail to address important medical decisions common at the end of life. Further work is needed to identify potential barriers to AD use in HF patients, and to determine whether their use has any impact on patient outcomes, including end of life resource utilization.

Background: Guidelines recommend involvement of palliative care (PC) for patients with cardiovascular (CV) disease and their families. Little is known about the current integration of PC and CV services. Research Objectives: Our national survey aimed to describe current practices and to identify benefits, challenges, and barriers with collaboration. Methods: Qualitative content analysis of open-response questions in an investigator-developed electronic survey study of CV and PC providers (MDs, NPs, PAs, and other allied health) using email listservs, social media, and crowdsourcing. Frequencies were tabulated using SAS statistical software. Results: Of 134 respondents, most were physicians (n=56, 57%) or advanced practice RNs or PAs (n=37, 28%), from 52 U.S. institutions, representing 33 states. The most common care for which PC was integrated were mechanical circulatory support, advanced heart failure, and heart transplantation; the least common care for which PC was integrated were TAVR, ECMO, and pulmonary hypertension. Integrated practice (n=80, 61%), PC identification of goals of care (n=20, 15%) and PC aid in patient/family communication (n=15, 11%) were the most commonly identified as positives in current practice. PC provider workforce (n=22, 16%), underutilization of PC referrals (n=20, 15%), late disease PC referral (n=19, 14%), and fundamental knowledge deficit of specialty scope (n=18, 14%) were most frequently identified as challenges. Other barriers specifically noted were underdeveloped health infrastructure and limited allocated resources (n=23,17%) and mis-/negative perception of services (n=15, 11%). Conclusion: PC and CV collaboration occurs for a high proportion of CV patients and is viewed as overwhelming positive, despite the challenges of limited PC specialists availability, underdeveloped healthcare infrastructure, limited understanding of specialty practice, and late referrals. Priorities includes increasing PC provider availability, expanding knowledge of PC services, educating providers on models of collaboration, and improving institutional support.

9592 Background: Palliative care (PC) is an essential part of the continuum of care for cancer (CA) patients (pts). Little is known about the aggregate characteristics and survival of pts receiving inpatient palliative care consultation (PCC). Methods: We reviewed data prospectively collected on patients seen by the Palliative Care Inpatient Consult Service at Mayo Clinic - Rochester from 2003–2008. Demographics, consult characteristics, and survival were analyzed. Kaplan-Meier survival curves and a Cox model of survival were produced. Results: 1794 total patients were seen over the five year period. Cancer is the most common primary diagnosis (47%). Growth in annual PCC has risen dramatically (113 in 2003 vs. 414 in 2007) despite stable total hospital admissions. Patient are predominantly men (52% vs. 48%, p=0.02); median age is 76. General medicine, medical cardiology, and medical intensive care unit services refer most often. Most frequent issues addressed are goals of care, dismissal planning, and pain control (29%, 19%, 17%). PCC in actively dying pts have increased with 27% of all non-operating room, non-trauma in-hospital deaths being seen. Although CA pts have the highest median survival after PCC vs. other diagnoses (17 days, p = 0.018), we observed a five-year trend of decreasing survival from admission to death and PCC to death. Median time from admission to death in CA pts is 36 days in 2003 and 19 days in 2008 (p<0.01). Median time from PCC to death is 33 versus 11.5 days (p<0.01). Despite this, median hospital length of stay and time from PCC to discharge have remained fixed at 8 and 2.5 days, respectively. A Cox model of survival to discharge and <6 months survival (hospice eligibility) shows hospital length of stay, time from consult to discharge, and dismissal location from hospital are all prognostic factors. Conclusions: Survival window for PC intervention for CA pts is lessening. With the trend of shorter survival after PCC, PC professionals have little over two days to implement a comprehensive, ongoing care plan. This highlights the importance of earlier outpatient palliative care involvement with advanced cancer patients and families. No significant financial relationships to disclose.

18552 Background: We reviewed Palliative Care Consultation Service (PCCS) referrals to attempt to promote earlier referrals, and to improve overall patient care. Methods: Eligibility for PCCS referral is life expectancy of one year or less. Data was collected prospectively on the first 461 referrals (452 individual patients) over the initial 30-month period (January 1, 2003 to July 1, 2005). Additional factors were retrospectively abstracted from documentation. Kaplan-Meier survival analysis was then performed. Results: 452 patients were seen (mean age 71.9 years), and 387 (86%) have died. Median length of inpatient stay was 8 days, with PCCS consultation requested 3 days prior to discharge. 107 patients (24%) died prior to hospital discharge. 345 patients survived to discharge, 236 (68%) died within 3 months, and 262 (76%) died within 6 months. Median survival from consultation to death was 12 days and after hospital discharge was 6 days. Secondary analysis determined that patients with malignancy had longer median survival from discharge to death than those with other diagnoses (11 days versus 3 days, p = 0.025). Median survival was longer with referrals from general surgery and surgical specialties (37 days and 8 days, respectively), compared to hematology-oncology and critical care (2 days and 0 days, respectively). Conclusions: The primary goal of the PCCS is to provide symptom control and maximize quality of life at the end of life. These data suggest palliative care services are unnecessarily delayed until too late. Education is necessary to facilitate earlier PCCS intervention. Survival analysis suggests providers are more likely to consider PCCS involvement in patients with malignancy compared with other diseases. Critical care and hematology-oncology, showed the lowest median survivals. Education efforts must be focused on these areas. Programs are underway to identify eligible patients earlier in their disease process, and educate providers about key end-of-life services provided to patients and families. No significant financial relationships to disclose.