Faculty Bibliography

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.

OBJECTIVE: Congenital insensitivity to pain with anhidrosis (CIPA) is caused by mutations in the NKTR1 gene. This affects the development of nerve growth factor (NGF)-dependent neurons including sympathetic cholinergic neurons in the skin, causing anhidrosis. Cardiovascular and blood pressure regulation appears normal, but the integrity of sympathetic adrenergic neurons has not been tested. METHODS: We examined the effect of posture on blood pressure, heart rate, plasma concentration of catecholamines, vasopressin, endothelin, and renin activity in 14 patients with CIPA, 10 patients with chronically deficient sympathetic activity (pure autonomic failure), and 15 normal age-matched controls. RESULTS: In all 14 patients with CIPA, plasma norepinephrine levels were very low or undetectable and failed to increase when the patient was upright, yet upright blood pressure was well maintained. Plasma epinephrine levels were normal and increased when the patient was upright. Plasma renin activity also increased appropriately when the patient was upright and after furosemide-induced volume depletion. Nitric oxide-mediated endothelial function was intact. Patients with pure autonomic failure also had very low levels of plasma norepinephrine both supine and upright, but in contrast to patients with CIPA failed to maintain blood pressure upright. INTERPRETATION: The results indicate that postganglionic sympathetic neurons are severely depleted in CIPA, but chromaffin cells of the adrenal medulla are spared. This confirms the differential effect of NGF signaling for sympathetic neural and chromaffin cell development. The finding that patients with CIPA maintain blood pressure well on standing challenges current concepts of the role of norepinephrine in the regulation of arterial pressure. Ann Neurol 2015;77:743-752.

AIM: To describe the results of the process evaluation of an exercise counseling intervention using motivational interviewing (MI). BACKGROUND: Exercise can safely be incorporated into heart failure self-care, but many lack access to cardiac rehabilitation. One alternative is to provide exercise counseling in the clinical setting. METHODS: This process evaluation was conducted according to previously established guidelines for health promotion programs. This includes an assessment of recruitment and retention, implementation, and reach. RESULTS: Desired number of subjects were recruited, but 25% dropped out during study. Good fidelity to the intervention was achieved; the use of MI was evaluated with improvement in adherence over time. Dose included initial session plus 12 weekly phone calls. Subjects varied in participation of daily diary usage. Setting was conducive to recruitment and data collection. CONCLUSIONS: Evaluating the process of an intervention provides valuable feedback on content, delivery and fidelity.

BACKGROUND: Familial dysautonomia (FD) is a rare hereditary disease characterized by loss of afferent autonomic neural fiber signaling and consequent profound impairment of arterial baroreflex function and blood pressure regulation. Whether vascular endothelial dysfunction contributes to defective vasomotor control in this form of afferent autonomic failure is not known. METHODS: We assessed blood pressure response to orthostatic stress and vascular endothelial function with brachial artery reactivity testing in 34 FD subjects with afferent autonomic failure and 34 healthy control subjects. RESULTS: Forty-four percent of the afferent autonomic failure subjects had uncontrolled hypertension at supine rest (median systolic blood pressure = 148mm Hg, interquartile range (IQR) = 144-155mm Hg; median diastolic blood pressure = 83mm Hg, IQR = 78-105mm Hg), and 88% had abnormal response to orthostatic stress (median decrease in systolic blood pressure after upright tilt = 48mm Hg, IQR = 29-61mm Hg). Flow-mediated brachial artery reactivity did not differ in subjects with afferent autonomic failure vs. healthy control subjects (median = 6.00%, IQR = 1.86-11.77%; vs. median = 6.27%, IQR = 4.65-9.34%; P = 0.75). In afferent autonomic failure subjects, brachial artery reactivity was not associated with resting blood pressure or the magnitude of orthostatic hypotension but was decreased in association with reduced glomerular filtration rate (r = 0.62; P < 0.001). CONCLUSIONS: Brachial artery reactivity was preserved in subjects with afferent autonomic failure despite the presence of marked blood pressure dysregulation. Comorbid renal dysfunction was associated with reduced brachial artery reactivity.

BACKGROUND: Treatment of acute heart failure in the emergency department (ED) or observation unit is an alternative to hospitalization. Both ED management and observation unit management have been associated with reduced costs and may be used to avoid penalties related to rehospitalizations. The purpose of this study was to examine trends in ED visits for heart failure and disposition following such visits. METHODS: We used the National Hospital Ambulatory Medical Care Survey, a representative sample of ED visits in the United States, to estimate rates and characteristics of ED visits for heart failure between 2002 and 2010. The primary outcome was the discharge disposition from the ED. Regression models were fit to estimate trends and predictors of hospitalization and admission to an observation unit. RESULTS: The number of ED visits for heart failure remained stable over the period, from 914,739 in 2002 to 848,634 in 2010 (annual change -0.7%, 95% CI -3.7% to +2.5%). Of these visits, 74.2% led to hospitalization, wheras 3.1% led to observation unit admission. The likelihood of hospitalization did not change during the period (adjusted prevalence ratio 1.00, 95% CI 0.99-1.01 for each additional year), whereas admission to the observation unit increased annually (adjusted prevalence ratio 1.12, 95% CI 1.01-1.25). We observed significant regional differences in likelihood of hospitalization and observation admission. CONCLUSIONS: The number of ED visits for heart failure and the high proportion of ED visits with subsequent inpatient hospitalization have not changed in the last decade. Opportunities may exist to reduce hospitalizations by increasing short-term management of heart failure in the ED or observation unit.