Citations

Introduction: In patients with heart failure, preferences for end-of-life (EOL) care and involvement in advance care planning can vary over their illness trajectory. The aim of this study was to compare EOL preferences by prognosis, assessed using the validated Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, in patients hospitalized with acute decompensated heart failure (ADHF). Hypothesis: EOL preferences and planning vary by prognosis. Methods: Between January 2014 and January 2016, Southeastern Minnesota residents hospitalized with ADHF at Mayo Clinic hospitals in Rochester, MN were prospectively recruited into an observational cohort study. Information on EOL preferences and advance care planning were assessed by patient questionnaire. MAGGIC risk scores and associated 1-year mortality estimates were calculated using patient characteristics at the time of hospital admission and stratified by quartile. The associations of EOL preferences/ planning and prognosis were examined using two sample t-tests and linear regression. Results: Among 400 patients (mean age 77.7 years, 46% female), predicted 1-year mortality ranged from 3.9-72.5% (median 22.5%). Patients with higher estimated mortality (worse prognosis) more often elected Do Not Resuscitate (DNR) status (p=0.001) and more often had an advanced directive (p<0.001, Table). No other differences in EOL preferences or planning by prognosis were observed. Conclusions: In community patients hospitalized with ADHF, resuscitation preferences and rates of completion of advance care planning documents varied with prognosis, though patient-clinician EOL discussions and awareness and attitudes about EOL options did not.

Introduction: Although national guidelines call on physicians to conduct regular conversations about end-of-life (EOL) care and planning with patients with heart failure (HF), research suggests that physicians often avoid these discussions. The aim of this study was to evaluate whether patients hospitalized with acute decompensated HF (ADHF) reported ever discussing their preferences for EOL care with their physicians. Methods: Between January 2014 and January 2016, Southeastern Minnesota residents hospitalized with ADHF at Mayo Clinic hospitals in Rochester, MN were prospectively recruited into an observational cohort study that included the administration of face-to-face questionnaires. Patients were asked questions regarding details of EOL discussions with their physicians, their preference for prognostic information, whether they had an advanced directive, attitudes about dying and hospice, and familiarity with palliative care and hospice. Results: Among 400 patients (mean age 77.7 years, 46% female, 48% preserved ejection fraction), only 68 (17.5%) reported previously discussing EOL wishes with their physician. Most patients (62.2%) indicated a preference to discuss their prognosis with their physician. Patients reporting prior EOL discussions were more often anemic (82.6% vs. 68.9%, p=0.022), hyponatremic (28.6% vs. 12.5%, p=0.002), and married (68.1% vs. 51.5%, p=0.012). They more often recognized the term ‘hospice’ (95.7% vs. 87.3%, p=0.045), had more favorable attitudes of dying and hospice (p=0.030), and more often had an advanced directive (83.6% vs. 67.7%, p=0.010). No other differences in demographics, comorbidity burden, HF characteristics, or in-hospital and 30-day outcomes were observed. Conclusions: Only 17.5% of patients hospitalized with ADHF reported previously discussing their preferences for EOL care with their physician. Patients reporting EOL discussions were more knowledgeable about EOL options and more likely to have completed advance care planning documents. Despite increasing recognition of the importance of these conversations, they are still occurring infrequently, and represent an important modifiable gap in the optimal longitudinal care of patients with HF.

Introduction: Perceived discrimination is known to play a role in the development of cardiovascular (CV) risk factors such as hypertension, but the association with CV outcomes is less clear. A recent report from a multi-ethnic cohort study found a modestly increased risk of CV disease in participants reporting discrimination. We explored this association in an African American (AA) cohort. Hypothesis: Greater perceived discrimination is associated with a higher risk of CV disease Methods: We examined CV outcomes among 5085 AAs in the Jackson Heart Study enrolled in 2000-2004 and followed through December 31, 2012. We stratified participants by quartiles of perceived everyday discrimination and estimated the associations with CV outcomes (all-cause mortality, incident coronary heart disease [CHD], incident stroke, and heart failure [HF] hospitalization) using Cox models. Results: Greater perceived discrimination was more common in participants who were younger, male, had higher education and income, a lower perceived standing in the community, worse perceived healthcare access, and fewer comorbidities. Over a median follow-up of 9.8 years (8.0 years for HF), 573 deaths, 193 incident CHD, 156 incident strokes, and 348 HF hospitalizations occurred. Prior to adjustment, greater perceived discrimination was associated with a lower risk of death, incident CHD, stroke, and HF hospitalization (Table). After adjustment for potential confounders, we found no association of perceived discrimination with incident CHD, stroke or HF hospitalization; however, a decrease in all-cause mortality risk with higher perceived discrimination persisted. Conclusions: We found no independent association of perceived discrimination with risk of incident CV disease or HF hospitalization and a paradoxical negative association with mortality in this AA population. The unexpected finding of a lower risk of death with greater perceived discrimination requires further study.

Introduction: As importantly underscored by the SPRINT Trial, innovative blood pressure (BP) lowering and multiorgan protective drugs are needed for treating hypertension (HTN). We engineered a Mayo Clinic designer atrial natriuretic peptide (ANP)-based drug, ZD100, which possesses a unique 12 amino acid (AA) carboxy-terminus (CT) extension while maintaining the N-terminus (NT) of ANP. ZD100 is more potent than ANP in reducing BP, inducing natriuresis and inhibiting aldosterone via pGC-A and its second messenger cGMP. To date, the in vivo actions of ZD100 in a model of essential HTN are undefined. Further, in attempt to enhance and/or minimize pGC-A activation, the importance of specific AAs in the CT and NT of ZD100 is unknown and is critical to define. Hypothesis: We hypothesize that ZD100 is a potent anti-HTN drug activating pGC-A/cGMP system and that specific AA variations in the CT and/or NT of ZD100 will modify the ability of activating pGC-A. Methods: Spontaneously hypertensive rats (SHRs) received intravenous (IV) ZD100 or vehicle and BP, plasma and urinary cGMP and the natriuretic effects were determined. We then engineered 15 strategic ZD100 variants (Vs) consisting of mutated peptides in the CT or NT or both. We stimulated HEK293 cells overexpressing pGC-A with ZD100 and the 15 Vs (10-8 M) and measured intracellular cGMP generation. Results: In SHRs, acute IV ZD100 reduced BP, increased plasma and urinary cGMP generation and induced natriuresis demonstrating efficacy in HTN. In vitro, we found two more potent pGC-A activators (+100% cGMP activation) only among the CT-only mutated ZD100 Vs. Importantly, key mutations of either the CT or NT resulted in 6 loss-of-function Vs identifying importance of peptide-receptor dependency. Conclusions: We demonstrate for the first time in a genetic model of HTN that ZD100 reduces BP, activates systemic and renal pGC-A/cGMP and induces natriuresis. Enhanced or reduced pGC-A activation with targeted AA mutations in the CT and NT of ZD100 provides key structure function insights into ZD100 which may lead to next generation ZD100 therapeutic peptides. These findings support ZD100 as a novel peptide therapeutic strategy for HTN and will help guide the selection of best-in-class ZD100 analogues.

Introduction: The prevalence of cardiac implantable electronic devices (CIED) is steadily increasing. Accordingly, the frequency of CIED extraction has also increased. Occasionally, safe retrieval of all CIED components is not feasabile and lead fragments are left behind. Little is known about the safety and diagnostic accuracy of MRI in patients with retained CIED fragments. Methods: Two hundred consecutive patients were identified as having undergone orthotopic heart transplantation (OHT) at our institution between April 2006 and December 2014. Chest x-rays immediately prior to OHT were reviewed for presence of CIED and chest x-rays immediately following OHT were reviewed for retained CIED fragments. MRI performed after OHT in patients with retained CIED fragments were inspected for image quality and procedural safety. The most recent chest x-ray in patients with retained CIED fragments subjected to MRI was reviewed for change in fragment position. Results: One hundred seventy-eight of 200 patients (89%) had CIED prior to OHT. All patients with CIED had surgical device extraction at the time of OHT. Of these, 29 patients (12%) had retained CIED fragments after OHT, the majority of which (23/29) were ICD coil fragments located in the superior vena cava, brachiocephalic or subclavian vein. Ten patients with retained CIED fragments underwent a total of 28 MRI after OHT. No patient safety issues were identified during MRI acquisition, and all MRI images were of diagnostic quality. There were no changes in the position of CIED fragments following MRI. Conclusions: Diagnostic MRI can be safely performed in patients with retained CIED fragments after incomplete device extraction. Adherence of the ICD coil to the vessel wall due to fibrosis has been well described and is a common impediment to complete device extraction. Retrieval of these fragments prior to MRI does not appear warranted given the demonstrated safety and preserved MRI image quality in this population.